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| Gene Symbol | TP53 | ||||||||||
| Synonyms | BCC7 | BMFS5 | LFS1 | P53 | TRP53 | ||||||||||
| Gene Description | TP53, tumor protein p53, is a tumor suppressor (PMID: 30562755) and oncogene (PMID: 30577483) involved in cell cycle arrest and apoptosis, and is the most frequently mutated gene in cancer (PMID: 10065147, PMID: 22713868). TP53 germline mutations are common in Li-Fraumeni syndrome (PMID: 30239254) and somatic missense mutations are frequent in almost all cancer types (PMID: 30224644) and are also implicated in chemoresistance (PMID: 9927204, PMID: 24065105, PMID: 27066457). | ||||||||||
| ACMG Incidental List v3.0: |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | Axitinib + M8891 | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Inlyta (axitinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | Cabozantinib + M8891 | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Cometriq (Cabometyx, cabozantinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |
| TP53 wild-type VHL inact mut | renal cell carcinoma | sensitive | M8891 + Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, M8891 and Sutent (sunitinib) combination treatment resulted in improved tumor growth inhibition compared to monotherapies in patient-derived xenograft (PDX) models of TP53 wild-type renal cell carcinoma harboring VHL inactivating mutations (PMID: 37940144). | 37940144 |
| TP53 del | lung cancer | resistant | M8891 | Preclinical - Cell culture | Actionable | In a preclinical study, knockout of TP53 conferred resistance to M8891 in a lung cancer cell line as demonstrated by loss of inhibition of colony formation in culture (PMID: 37940144). | 37940144 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is indicated in guidelines as first-line, second-line, or third-line therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is indicated in guidelines as first-line, second-line, or third-line therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Obinutuzumab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is indicated in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Obinutuzumab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is indicated in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss and for patients with relapsed or refractory disease after prior BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 wild-type | meningioma | sensitive | CEP1347 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CEP-1347 induced apoptosis, inhibited viability, and decreased colony formation in a TP53 wild-type meningioma cell line in culture and inhibited tumor growth in a cell line xenograft model (PMID: 37509605). | 37509605 |
| TP53 E180R | acute myeloid leukemia | sensitive | Cytarabine + Doxorubicin | Preclinical | Actionable | In a preclinical study, the combination of Cytosar-U (cytarabine) and Adriamycin (doxorubicin) inhibited tumor growth and increased survival (p<0.0001) compared to control treatment in a mouse model of acute myeloid leukemia harboring TP53 E177R (corresponding to E180R in human) (PMID: 34907344). | 34907344 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Pirtobrutinib | Guideline | Actionable | Jaypirca (pirtobrutinib) is included in guidelines as second-line or third-line therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor and Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Pirtobrutinib | Guideline | Actionable | Jaypirca (pirtobrutinib) is included in guidelines as second-line or third-line therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss and for patients with relapsed or refractory disease after prior BTK inhibitor and Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type, ALK-amplified neuroblastoma cell line in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
| ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line with ALK amplification in culture (PMID: 36602782). | 36602782 |
| ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782). | 36602782 |
| ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |
| ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Case Reports/Case Series | Actionable | In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782). | 36602782 |
| ALK F1174C TP53 wild-type | neuroblastoma | resistant | Idasanutlin + Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma harboring ALK F1174C was resistant to combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) (PMID: 36602782). | 36602782 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) resulted in an additive effect on tumor growth inhibition with complete remission in a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma with ALK amplification and overexpression (PMID: 36602782). | 36602782 |
| TP53 P72R | breast cancer | predicted - sensitive | Cyclophosphamide + Doxorubicin + Fluorouracil | Phase I | Actionable | In a Phase I trial, breast cancer patients harboring TP53 P72R were reported to have a better response to anthracycline-based neoadjuvant therapies, including Adriamycin (doxorubicin) in combination with Cytoxan (cyclophosphamide) and Adrucil (fluorouracil) (PMID: 16243804). | 16243804 |
| TP53 P72R | breast cancer | predicted - sensitive | Cyclophosphamide + Epirubicin + Fluorouracil | Phase I | Actionable | In a Phase I trial, breast cancer patients harboring TP53 P72R were reported to have a better response to anthracycline-based neoadjuvant therapies, including Ellence (epirubicin) in combination with Cytoxan (cyclophosphamide) and Adrucil (fluorouracil) (PMID: 16243804). | 16243804 |
| TP53 P72R | breast cancer | predicted - sensitive | Cyclophosphamide + Fluorouracil + Pirarubicin | Phase I | Actionable | In a Phase I trial, breast cancer patients harboring TP53 P72R were reported to have a better response to anthracycline-based neoadjuvant therapies, including pirarubicin in combination with Cytoxan (cyclophosphamide) and Adrucil (fluorouracil) (PMID: 16243804). | 16243804 |
| TP53 wild-type | acute myeloid leukemia | predicted - sensitive | Siremadlin | Phase I | Actionable | In a Phase I trial, Siremadlin (HDM201) treatment demonstrated safety and resulted in overall response rates of 4.2% (1/24), 20% (3/15), and 22.2% (6/27) for the recommended expansion doses of 120 mg, 250 mg, and 45 mg, respectively, in patients with TP53 wild-type acute myeloid leukemia (PMID: 34862243; NCT02143635). | 34862243 |
| TP53 del | colorectal cancer | predicted - sensitive | MK-8745 | Preclinical - Cell culture | Actionable | In a preclinical study, MK-8745 treatment resulted in polyploidy in TP53-null colorectal cancer cells in culture (PMID: 22293494). | 22293494 |
| TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | BI 907828 + Ezabenlimab | Phase I | Actionable | In a Phase I trial, Ezabenlimab (BI 754091) and BI 907828 combination therapy demonstrated safety in patients with TP53 wild-type advanced solid tumors (n=9), and resulted in a partial response (PR) in 2 patients with biliary tract carcinoma, 1 urothelial carcinoma patient, and 1 myxoid liposarcoma patient, an unconfirmed PR in an intrahepatic cholangiocarcinoma patient, and stable disease in 4 patients with liposarcoma or gastric cancer (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3095; NCT03964233). | detail... |
| TP53 Y220C | prostate cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in unconfirmed partial responses in two patients with prostate cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
| TP53 Y220C | colorectal cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in an unconfirmed partial response in a patient with colorectal cancer harboring TP53 Y220C (J Clin Oncol 40,no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
| TP53 Y220C | breast cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in a partial response in a patient with breast cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
| TP53 Y220C | lung small cell carcinoma | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in a partial response in a patient with small cell lung cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) and Rituxan (rituximab) combination therapy is included in the guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 33091559; ESMO.org). | detail... 33091559 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is included in the guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 33091559; ESMO.org). | detail... 33091559 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) and Gazyva (obinutuzumab) combination therapy is included in the guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 33091559; ESMO.org). | 33091559 detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is included in the guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 33091559; ESMO.org). | 33091559 detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is included in the guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 33091559; ESMO.org). | 33091559 detail... |
| NRAS mut TP53 mut | colorectal cancer | no benefit | Adavosertib | Phase II | Actionable | In a Phase II trial (FOCUS4-C), Adavosertib (AZD1775) treatment was well-tolerated and resulted in an advantage in progression-free survival (PFS, HR 0.40, p=0.0051) but not overall survival (0.92, p=0.93) compared to active monitoring in patients with metastatic colorectal cancer harboring both RAS and TP53 mutations, however, patients with NRAS mutations or KRAS non-G12/G13 mutations did not benefit from Adavosertib (AZD1775) treatment in subgroup PFS analysis (PMID: 34538072). | 34538072 |
| JAK2 V617F TP53 R248W | acute myeloid leukemia | predicted - sensitive | IMG-7289 + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with Jakafi (ruxolitinib) and IMG-7289 led to synergistic inhibition of colony formation and apoptosis induction in an acute myeloid leukemia cell line harboring JAK2 V617F and TP53 R248W in culture (PMID: 31723778). | 31723778 |
| JAK2 V617F TP53 R248W | acute myeloid leukemia | predicted - sensitive | IMG-7289 | Preclinical - Cell culture | Actionable | In a preclinical study, IMG-7289 treatment led to inhibition of colony formation, increased apoptosis and induction of cell cycle arrest in an acute myeloid leukemia cell line harboring JAK2 V617F and TP53 R248W in culture (PMID: 31723778). | 31723778 |
| TP53 mutant | high grade glioma | predicted - sensitive | KU-60019 + Radiotherapy | Preclinical | Actionable | In a preclinical study, KU-60019 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, and the combination prolonged survival in syngeneic intracranial tumor models compared to radiation alone (PMID: 29769307). | 29769307 |
| TP53 M237I | high grade glioma | sensitive | KU-60019 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, KU-60019 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 M237I in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 29769307). | 29769307 |
| TP53 mutant | high grade glioma | no benefit | AZ31 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ31 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, but failed to radiosensitize tumors in syngeneic mouse models due to poor blood-brain barrier permeability (PMID: 29769307). | 29769307 |
| TP53 R248W | colon carcinoma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in colon carcinoma cells harboring TP53 R248W compared to radiotherapy alone in culture, resulting in increased mitotic catastrophe; however, wild-type TP53 cells were more sensitive to the treatment combination than TP53 R248W mutant cells (PMID: 29769307). | 29769307 |
| TP53 wild-type | colon carcinoma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in TP53 wild-type colon carcinoma cells compared to radiotherapy alone in culture, and wild-type TP53 cells were more sensitive to the treatment combination than TP53 mutant cells (PMID: 29769307). | 29769307 |
| TP53 Q331* | lung non-small cell carcinoma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy and demonstrated increased tumor growth inhibition and prolonged survival compared to radiation alone in an intracranial cell line xenograft model of non-small cell lung cancer brain metastasis harboring TP53 Q331* (PMID: 29769307). | 29769307 |
| TP53 D281G | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 D281G, resulting in significantly increased survival (P=0.0015) in intracranial cell line xenograft models compared to radiotherapy alone (PMID: 29769307). | 29769307 |
| TP53 mutant | high grade glioma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in TP53 mutant mouse glioma cells, resulting in reduced cell survival and impaired DNA damage response in culture, and prolonged survival and significantly increased apoptosis of tumor cells compared to normal brain cells (p<0.01) in syngeneic intracranial tumor models (PMID: 29769307). | 29769307 |
| TP53 dec exp | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, shRNA knock-down of TP53 in malignant glioma cells enhanced sensitivity to the combination of AZ32 and radiation compared to TP53 wild-type cells in culture, and resulted in a greater decrease in cell survival and increased mitotic failure compared to either treatment treatment alone (PMID: 29769307). | 29769307 |
| TP53 M237I | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 M237I in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 29769307). | 29769307 |
| TP53 R175H | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 R175H in culture, resulting in a greater decrease in cell survival and increased mitotic failure compared to radiation treatment alone (PMID: 29769307). | 29769307 |
| TP53 C238S | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 C238S in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 29769307). | 29769307 |
| TP53 wild-type | high grade glioma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in TP53 wild-type malignant glioma cell lines in culture, however, the effect was smaller compared to the effects in TP53 mutant cell lines (PMID: 29769307). | 29769307 |
| TP53 Y220C | Advanced Solid Tumor | predicted - sensitive | PC14586 | Phase I | Actionable | In a Phase I trial, PC14586 treatment demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring TP53 Y220C, and resulted in 5 partial responses amongst 21 evaluable patients including confirmed partial responses in one small cell lung cancer and one breast cancer patient, and unconfirmed partial responses in one colorectal cancer and two prostate cancer patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
| TP53 Y220C | Advanced Solid Tumor | predicted - sensitive | PC14586 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PC14586 treatment reactivated Tp53 function and resulted in cell cycle arrest in cancer cell lines harboring TP53 Y220C in culture, and led to complete cure in 80% of syngeneic xenograft models (AACR Annual Meeting Apr 2021, Session MS.LBA01, Abstract # LB006). | detail... |
| TP53 Y220C | stomach cancer | predicted - sensitive | PC14586 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PC14586 treatment reactivated Tp53 function, resulted in 80% tumor regression after 3 weeks in cell line xenograft models of gastric cancer harboring TP53 Y220C (AACR Annual Meeting Apr 2021, Session MS.LBA01, Abstract # LB006). | detail... |
| EML4 - ALK TP53 V274fs | lung non-small cell carcinoma | sensitive | Alectinib + Ixazomib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture and resulted in tumor regression in cell line xenograft models, with 3/8 achieving complete tumor regression (PMID: 33310890). | 33310890 |
| EML4 - ALK TP53 Q331* | lung non-small cell carcinoma | sensitive | Alectinib + Ixazomib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture (PMID: 33310890). | 33310890 |
| EML4 - ALK TP53 V274fs | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274fs were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). | 33310890 |
| EML4 - ALK TP53 V274fs | lung non-small cell carcinoma | resistant | Alectinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274* were resistant to treatment with Alecensa (alectinib), demonstrating cell growth in culture and tumor growth in cell line xenograft models (PMID: 33310890). | 33310890 |
| EML4 - ALK TP53 Q331* | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). | 33310890 |
| EML4 - ALK TP53 Q331* | lung non-small cell carcinoma | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33310890). | 33310890 |
| BRAF V600E TP53 C176R | pancreatic adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic pancreatic adenocarcinoma harboring BRAF V600E and TP53 C176R was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) and achieved radiographic and biochemical responses with stabilization or reduction of lesions in the pancreas, lung, and liver, and remained on treatment despite progression of a single liver lesion after 8 months (PMID: 33250737). | 33250737 |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as first line therapy and second line therapy and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Lenalidomide + Rituximab | Guideline | Actionable | Revlimid (lenalidomide) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Lenalidomide + Rituximab | Guideline | Actionable | Revlimid (lenalidomide) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib | Guideline | Actionable | Zydelig (idelalisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib | Guideline | Actionable | Zydelig (idelalisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab | Guideline | Actionable | Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab | Guideline | Actionable | Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Rituximab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is indicated in the guidelines as first-line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Rituximab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is indicated in the guidelines as first-line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Alemtuzumab + Rituximab | Guideline | Actionable | Campath (alemtuzumab) combined with Rituxan (rituximab) is indicated in guidelines as therapy for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation who received prior treatment with a BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Alemtuzumab + Rituximab | Guideline | Actionable | Campath (alemtuzumab) combined with Rituxan (rituximab) is indicated in guidelines as therapy for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss who received prior treatment with a BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 mutant | esophagus adenocarcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited phosphorylation of Wee1 and Cdk1, and reduced viability of TP53-mutant esophageal adenocarcinoma cells in culture, and led to partial tumor growth delay in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus squamous cell carcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited viability of TP53-mutant esophageal squamous cell carcinoma cells in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus squamous cell carcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal squamous cell carcinoma cells to radiation therapy, resulting in decreased colony formation in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus adenocarcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal adenocarcinoma cells to radiation therapy, resulting in inhibition of phosphorylation of Wee1 and Cdk1, reduced colony formation, and increased DNA damage and mitotic cell death in culture, and tumor growth inhibition and regression in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 wild-type | gastric adenocarcinoma | no benefit | Adavosertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment did not sensitize TP53 wild-type gastric adenocarcinoma cells to radiation therapy in culture (PMID: 32220892). | 32220892 |
| TP53 I255N | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Patient cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis of leukemic blast cells and decreased cell viability in patient-derived acute myeloid leukemia cells harboring TP53 I255N in culture (PMID: 32945487). | 32945487 |
| TP53 C242fs | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis, decreased cell viability, altered cell cycle progression, elevated expression of Tp53 target genes, and increased Tp53 nuclear localization in an acute myeloid leukemia cell line harboring TP53 C242fs in culture (PMID: 32945487). | 32945487 |
| TP53 R248Q | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis, decreased cell viability, elevated expression of Tp53 target genes, and increased Tp53 nuclear localization in an acute myeloid leukemia cell line harboring TP53 R248Q in culture (PMID: 32945487). | 32945487 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | CG-806 | Case Reports/Case Series | Actionable | In a Phase I trial, CG-806 treatment was well-tolerated, and a patient with chronic lymphocytic leukemia harboring a TP53 mutation stayed on treatment for more than 8 cycles (25th Annual Congress of EHA (Jun 2020), Abstract EP711; NCT03893682). | detail... |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Azacitidine + Hu5F9-G4 | Phase I | Actionable | In a Phase Ib trial, Magrolimab (Hu5F9-G4) and Vidaza (azacitidine) combination therapy was well tolerated, and resulted in complete response in 42% (5/12), complete response with incomplete hematologic recovery in 33% (4/12), and stable disease in 17% (2/12) of patients with acute myeloid leukemia harboring TP53 mutations and unfit for chemotherapy (J Clin Oncol 38: 2020 (suppl; abstr 7507); NCT03248479). | detail... |
| TP53 mutant | endometrial carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 2 of the patients achieved PR had endometrial carcinoma (EC), and TP53 mutations were identified in 1 of the EC patients with biopsy available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | ovarian carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 4 of the patients achieved PR had ovarian carcinoma (OVC), and TP53 mutations were identified in 2 of the OVC patients with biopsies available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 inact mut | lung non-small cell carcinoma | not predictive | Osimertinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with non-small cell lung cancer harboring inactivating TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (5 vs 11.5 months, p=0.0005) compared to patients with wild-type TP53 (PMID: 31839416). | 31839416 |
| TP53 mutant | lung non-small cell carcinoma | not predictive | Osimertinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with non-small cell lung cancer harboring TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (6.5 vs 11.5 months, p=0.0029) compared to patients with wild-type TP53 (PMID: 31839416). | 31839416 |
| TP53 R181E | Advanced Solid Tumor | sensitive | Doxorubicin + RG7112 | Preclinical - Cell culture | Actionable | In a preclinical study, RG7112 (RO5045337) and Adriamycin (doxorubicin) combination treatment induced cytotoxicity in transformed mouse cells expressing TP53 R181E in culture (PMID: 31483066). | 31483066 |
| TP53 R181E | Advanced Solid Tumor | sensitive | Doxorubicin + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Idasanutlin (RG7388) and Adriamycin (doxorubicin) combination treatment induced cytotoxicity in transformed mouse cells expressing TP53 R181E in culture (PMID: 31483066). | 31483066 |
| TP53 R181E | Advanced Solid Tumor | sensitive | Doxorubicin + SAR405838 | Preclinical - Cell culture | Actionable | In a preclinical study, SAR405838 and Adriamycin (doxorubicin) combination treatment induced cytotoxicity in transformed mouse cells expressing TP53 R181E in culture (PMID: 31483066). | 31483066 |
| TP53 R181E | Advanced Solid Tumor | sensitive | Doxorubicin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 and Adriamycin (doxorubicin) combination treatment inhibited proliferation and viability of transformed mouse cells expressing TP53 R181E in culture (PMID: 31483066). | 31483066 |
| TP53 R181E | lung adenocarcinoma | sensitive | Doxorubicin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, a lung adenocarcinoma cell line expressing TP53 R181E demonstrated enhanced sensitivity to Adriamycin (doxorubicin) treatment when combined with Nutlin-3, and induced apoptosis in culture (PMID: 31483066). | 31483066 |
| TP53 R175P | lung adenocarcinoma | no benefit | Doxorubicin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 and Adriamycin (doxorubicin) combination treatment did not induce apoptosis in a lung adenocarcinoma cell line expressing TP53 R175P in culture (PMID: 31483066). | 31483066 |
| TP53 R181L | lung adenocarcinoma | sensitive | Doxorubicin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, a lung adenocarcinoma cell line expressing TP53 R181L demonstrated enhanced sensitivity to Adriamycin (doxorubicin) treatment when combined with Nutlin-3, and induced apoptosis in culture (PMID: 31483066). | 31483066 |
| TP53 R181E | Advanced Solid Tumor | no benefit | Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 treatment did not reduce cell proliferation and viability in transformed mouse cells expressing TP53 R181E in culture (PMID: 31483066). | 31483066 |
| TP53 Y220C | hepatocellular carcinoma | sensitive | SLMP53-2 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of SLMP53-2 and Nexavar (sorafenib) inhibited growth of a hepatocellular carcinoma cell line harboring TP53 Y220C in culture, and resulted in increased inhibition compared to Nexavar (sorafenib) alone (PMID: 31405179). | 31405179 |
| TP53 Y220C | hepatocellular carcinoma | sensitive | SLMP53-2 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with SLMP53-2 induced cell-cycle arrest and apoptosis and inhibited growth, and resulted in restored Tp53 transcriptional activity in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture, and inhibited tumor growth in xenograft models (PMID: 31405179). | 31405179 |
| TP53 Y220C | breast ductal carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 treatment inhibited growth of a breast ductal carcinoma cell line harboring TP53 Y220C and resulted in increased expression of the Tp53 targets MDM2, p21, and KILLER and decreased expression of Survivin and VEGF in culture (PMID: 31405179). | 31405179 |
| TP53 G245S | lung non-small cell carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 inhibited growth of a non-small cell lung carcinoma cell line expressing TP53 G245S in culture (PMID: 31405179). | 31405179 |
| TP53 Y220C | lung non-small cell carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 inhibited growth of a non-small cell lung carcinoma cell line expressing TP53 Y220C in culture (PMID: 31405179). | 31405179 |
| TP53 R175H | lung non-small cell carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 inhibited growth of a non-small cell lung carcinoma cell line expressing TP53 R175H in culture (PMID: 31405179). | 31405179 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib + Obinutuzumab | Guideline | Actionable | Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is indicated in the guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib + Obinutuzumab | Guideline | Actionable | Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is indicated in the guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | ovarian cancer | sensitive | AZD7648 | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of ovarian cancer harboring a TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| TP53 mutant | ovarian cancer | predicted - sensitive | Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, Lynparza (olaparib) treatment inhibited tumor growth but did not induce regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring wild-type ATM and TP53 mutation (PMID: 31699977). | 31699977 |
| TP53 mutant | ovarian cancer | predicted - sensitive | AZD7648 + Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment induced tumor regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as first line therapy and second line therapy and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Phase I | Actionable | In a Phase I trial, Brukinsa (zanubrutinib) treatment resulted in an overall response rate of 100% (16/16) in patients with CLL/SLL harboring del (17p) or TP53 mutations (PMID: 31340982; NCT02343120). | 31340982 |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Duvelisib | Guideline | Actionable | Copiktra (duvelisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Duvelisib | Guideline | Actionable | Copiktra (duvelisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | acute myeloid leukemia | sensitive | Decitabine | Guideline | Actionable | Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 wild-type | multiple myeloma | predicted - sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 50% (5/10) of patients with TP53 wild-type multiple myeloma (PMID: 31359240; NCT01723020). | 31359240 |
| TP53 wild-type | estrogen-receptor positive breast cancer | predicted - sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 83.3% (10/12) of patients with TP53 wild-type ER-positive breast cancer (BC), with a median duration of 2.0 months in ER-positive, PR-positive BC, 1.4 months in ER-positive, PR-negative BC, and one patient achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). | 31359240 |
| TP53 wild-type | liposarcoma | predicted - sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 100% (10/10) of patients with TP53 wild-type well-differentiated liposarcomas (WDLPS) and 70% (7/10) of patients with TP53 wild-type de-differentiated liposarcomas, with median duration of 3.9 and 2.0 months respectively, and one patient with WDLPS achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). | 31359240 |
| NRAS mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| BRAF mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| ROS1 rearrange ROS1 L2026M TP53 P278H | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired two mutations, ROS1 L2026M and TP53 P278H (PMID: 30978502; NCT02183870). | 30978502 |
| ROS1 rearrange TP53 mut | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a Phase II clinical trial, treatment with Xalkori (crizotinib) demonstrated a shorter median progression-free survival in patients with non-small cell lung cancer co-harboring a ROS1 rearrangement and TP53 mutation compared to patients with a ROS1 rearrangement and wild-type TP53 (7 vs. 24.1 months; p=0.022) (PMID: 30978502; NCT02183870). | 30978502 |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | CG-806 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring TP53 mutations were sensitive to CG-806 in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1323). | detail... |
| TP53 inact mut | prostate cancer | no benefit | Abiraterone | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). | 30209161 |
| TP53 inact mut | prostate cancer | no benefit | Enzalutamide | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). | 30209161 |
| ATM T1200Lfs*7 NRAS Q61K TP53 R213* | sarcoma | predicted - resistant | Olaparib | Case Reports/Case Series | Actionable | In a clinical case study, Lynparza (olaparib) treatment resulted in rapid disease progression in a patient with high-grade sarcoma harboring ATM T1200Lfs*7, NRAS Q61K, and TP53 R213* (PMID: 29304353). | 29304353 |
| TP53 mutant | Advanced Solid Tumor | sensitive | Unspecified VEGFR inhibitor | Clinical Study - Cohort | Actionable | In a clinical study, VEGF/VEGFR inhibitor treatment resulted in improved rates of response (stable disease over 6 months/partial/complete response, 31% vs 7%), time-to-treatment failure, and overall survival (both p<0.01) compared to control in patients with TP53 mutant advanced solid tumors (n=106), but not in patients with TP53 wild-type tumors (n=82) (PMID: 27466356). | 27466356 |
| TP53 G244S | mantle cell lymphoma | predicted - sensitive | Ibrutinib + Rituximab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-nodal leukemic mantle cell lymphoma harboring TP53 G244S, as well as KMT2A V2593A and BCOR S830Cfs*6, achieved complete remission (CR) with no evident minimum residual disease after 5 months of combined Rituxan (rituximab) and Imbruvica (ibrutinib) therapy, and following subsequent autologous stem-cell transplantation remained in CR beyond 18 months (PMID: 30559058). | 30559058 |
| TP53 loss | mantle cell lymphoma | predicted - sensitive | Ibrutinib + Rituximab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-nodal leukemic mantle cell lymphoma with TP53 loss, as well as a CCND1 translocation, had a rapid response to combined Rituxan (rituximab) and Imbruvica (ibrutinib) therapy, achieved a complete remission (CR) within 6 months, underwent autologous stem-cell transplantation, and remained in CR 18 months thereafter (PMID: 30559058). | 30559058 |
| TP53 loss | mantle cell lymphoma | no benefit | Bendamustine + Rituximab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-nodal leukemic mantle cell lymphoma with TP53 loss, as well as a CCND1 translocation, had no response to combined Rituxan (rituximab) and Treanda (bendamustine) therapy, and had a doubling of white blood cells during two cycles of treatment (PMID: 30559058). | 30559058 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Brigatinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Alectinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Ceritinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Crizotinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). | 30165392 |
| TP53 R248Q | colorectal cancer | predicted - sensitive | Napabucasin | Preclinical - Cell culture | Actionable | In a preclinical study, Napabucasin (BBI608) treatment reduced Stat3 phosphorylation and impaired wound healing in colorectal cancer cell lines expressing TP53 R248Q in culture (PMID: 30107178). | 30107178 |
| TP53 del | colorectal cancer | decreased response | Tanespimycin | Preclinical | Actionable | In a preclincal study, Tanespimycin (17-AAG) treatment of mutagen induced colorectal cancer in a genetic mouse model with biallelic loss of TP53 was less effective than treatment of mice bearing a single allele with a TP53 R248Q mutation (PMID: 30107178). | 30107178 |
| TP53 R248Q | colorectal cancer | sensitive | Tanespimycin | Preclinical | Actionable | In a preclincal study, Tanespimycin (17-AAG) treatment reduced p-Stat3 expression, induced apoptosis, and inhibited tumor growth of mutagen induced colorectal cancer in a genetic mouse model expressing TP53 R248Q (PMID: 30107178). | 30107178 |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 30% (3/10) of patients with acute myeloid leukemia harboring TP53 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| TP53 mutant | glioblastoma | sensitive | AZD1390 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53 mutant glioblastoma cells demonstrated increased sensitivity to radiosensitization by AZD1390 treatment compared to TP53 wild-type cells in culture (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). | detail... |
| TP53 wild-type | acute myeloid leukemia | sensitive | ALRN-6924 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ALRN-6924 inhibited growth of cells derived from patients with TP53 wild-type acute myeloid leukemia in culture, and inhibited leukemia cell growth, prolonged survival in cell line xenograft models (PMID: 29643228). | 29643228 |
| TP53 R248Q | acute myeloid leukemia | resistant | ALRN-6924 | Preclinical - Cell culture | Actionable | In a preclinical study, ALRN-6924 did not inhibit the growth of acute myeloid leukemia cells harboring TP53 R248Q in culture (PMID: 29643228). | 29643228 |
| TP53 loss | acute myeloid leukemia | resistant | ALRN-6924 | Preclinical - Cell culture | Actionable | In a preclinical study, ALRN-6924 did not inhibit the growth of TP53-null acute myeloid leukemia cells in culture (PMID: 29643228). | 29643228 |
| TP53 mutant | head and neck squamous cell carcinoma | predicted - sensitive | Buparlisib + Paclitaxel | Phase II | Actionable | In a Phase II (BERIL-1) trial, Buparlisib (BKM120) and Taxol (paclitaxel) combination treatment resulted in improved overall survival (HR=0.52) and prolonged progression-free survival (HR=0.45) in head and neck squamous cell carcinoma patients harboring TP53 mutations compared to TP53 wild-type patients (PMID: 29490986; NCT01852292). | 29490986 |
| TP53 mutant | sarcoma | predicted - sensitive | GDC-0575 + Gemcitabine | Phase I | Actionable | In a Phase I trial, GDC-0575 and Gemzar (gemcitabine) combination treatment resulted in a prolonged tumor response in 2 soft tissue sarcoma patients harboring TP53 mutations, and no response in a patient with TP53 wild-type tumor (PMID: 29409053; NCT01564251). | 29409053 |
| TP53 mutant | fibrous histiocytoma | predicted - sensitive | GDC-0575 + Gemcitabine | Preclinical - Pdx | Actionable | In a preclinical study, GDC-0575 and Gemzar (gemcitabine) combination treatment inhibited tumor growth, prolonged progression-free survival in patient-derived xenogrft (PDX) models of undifferentiated pleomorphic sarcoma (fibrous histiocytoma) (PMID: 29409053). | 29409053 |
| TP53 wild-type | salivary gland adenoid cystic carcinoma | predicted - sensitive | Cisplatin + SAR405838 | Preclinical - Pdx | Actionable | In a preclinical study, the combination of SAR405838 (MI-773) and Platinol (cisplatin) resulted in increased Tp53 and Mdm2 expression, and demonstrated improved efficacy over either agent alone in TP53 wild-type patient-derived xenograft (PDX) models of salivary gland adenoid cystic carcinoma, resulting in tumor regression without tumor rebound after cessation of therapy (PMID: 27550999). | 27550999 |
| RB1 K240Sfs*22 TP53 R248W | Her2-receptor negative breast cancer | predicted - resistant | Fulvestrant + Palbociclib | Case Reports/Case Series | Actionable | In a clinical case study, RB1 K240Sfs*22 and TP53 R248W were identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 5 months of Ibrance (palbociclib) and Faslodex (fulvestrant) combination treatment (PMID: 29236940). | 29236940 |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Rituximab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Rituximab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is indicated in the guidelines as first line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is indicated in the guidelines as first line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 inact mut | breast carcinoma | predicted - sensitive | CHIR-124 + SN-38 | Preclinical - Cell culture | Actionable | In a preclinical study, SN-38 and CHIR-124 demonstrated synergy in a breast carcinoma cell line with defective TP53, resulting in increased cell cycle arrest and apoptosis in culture (PMID: 17255282). | 17255282 |
| TP53 loss | colon cancer | sensitive | CHIR-124 + SN-38 | Preclinical - Cell culture | Actionable | In a preclinical study, a colon cancer cell line deficient in TP53 demonstrated increased sensitivity to sequential treatment with SN-38 and CHIR-124 compared to cells with wild-type TP53, resulting in increased apoptosis and micronucleation in culture (PMID: 17255282). | 17255282 |
| TP53 inact mut | breast carcinoma | predicted - sensitive | CHIR-124 + Irinotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, sequential treatment with Camptosaur (irinotecan) and CHIR-124 enhanced tumor growth inhibition compared to either agent alone in a breast carcinoma cell line xenograft model with defective TP53 (PMID: 17255282). | 17255282 |
| TP53 mutant | breast carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant breast carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 mutant | colon carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant colon carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 over exp | ovarian cancer | predicted - sensitive | HLA-A2 p53:264-272 vaccine | Phase I | Actionable | In a Phase I trial, the HLA-A2 p53:264-272 vaccine demonstrated safety and preliminary efficacy in patients with TP53 overexpressing ovarian cancer, resulting in a progression-free survival of 5.5 months and an overall survival of 40.4 months (PMID: 21927947). | 21927947 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial, Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy resulted in a response rate of 100% (14/14, 9 complete response, 5 partial response) in relapsed or refractory chronic lymphocytic leukemia (CLL) patients, and a response rate of 100% (16/16, 9 complete response, 7 partial response) in untreated patients with high-risk features including del 17p, TP53 mutations, and del 11q (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 429; NCT02756897). | detail... |
| TP53 loss | thymoma | predicted - resistant | Selinexor | Preclinical - Cell culture | Actionable | In a preclinical study, a thymoma cell line with TP53 loss demonstrated primary resistance to Selinexor (KPT-330) in culture, and reconstitution of TP53 expression resulted in increased Selinexor sensitivity (PMID: 28819023). | 28819023 |
| TP53 positive | ovarian cancer | predicted - sensitive | NU6027 + Temozolomide | Preclinical - Cell culture | Actionable | In a preclinical study, NU6027 enhanced the efficacy of Temodar (temozolomide) in ovarian cancer cells with mismatch repair activity and positive for TP53 in culture, demonstrating a 50% greater decrease in cell survival compared to Temodar (temozolomide) alone (PMID: 21730979). | 21730979 |
| TP53 P98fs TP53 R175C TP53 S215G | ovarian cancer | predicted - resistant | Adavosertib + Carboplatin | Case Reports/Case Series | Actionable | In a Phase II trial, Paraplatin (carboplatin) and Adavosertib (MK-1775) combination treatment resulted in disease progression in an ovarian cancer patient harboring TP53 P98fs, R175C, and S215G (PMID: 27998224; NCT01164995). | 27998224 |
| TP53 Y163* | ovarian cancer | predicted - sensitive | Adavosertib + Carboplatin | Case Reports/Case Series | Actionable | In a Phase II trial, Paraplatin (carboplatin) and Adavosertib (MK-1775) combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 Y163* (PMID: 27998224; NCT01164995). | 27998224 |
| TP53 mutant | ovarian cancer | predicted - sensitive | Adavosertib + Carboplatin | Phase II | Actionable | In a Phase II trial, Paraplatin (carboplatin) and Adavosertib (MK-1775) combination treatment resulted in an overall response rate of 43% (9/21), a median progression-free survival of 5.3 months and a median overall survival of 12.6 months in ovarian cancer patients harboring TP53 mutations (PMID: 27998224; NCT01164995). | 27998224 |
| TP53 wild-type | lung non-small cell carcinoma | sensitive | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, Roscovotine (seliciclib) induced substantial apoptosis in non-small cell lung carcinoma cells overexpressing wild-type TP53 in culture (PMID: 22862161). | 22862161 |
| TP53 Y234C | lung non-small cell carcinoma | decreased response | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 Y234C demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 A159V | lung non-small cell carcinoma | decreased response | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 A159V demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 P98A | lung non-small cell carcinoma | decreased response | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 P98A demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 Y220C | lung non-small cell carcinoma | resistant | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 Y220C were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 S215G | lung non-small cell carcinoma | resistant | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 S215G were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 R175H | lung non-small cell carcinoma | resistant | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 R175H were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 negative | lung non-small cell carcinoma | decreased response | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, TP53-null non-small cell lung carcinoma cells demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of a Phase I trial demonstrated non-small cell lung carcinoma (NSCLC) patients harboring either a TP53 mutation (n=15) or KRAS mutation (n=8) had greater progression free survival compared to NSCLC patients harboring wild-type TP53 or KRAS (n=15) (14.5mo vs 14.7mo vs 3.5mo, respectively) when treated with Keytruda (pembrolizumab) (PMID: 28039262). | 28039262 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | breast cancer | sensitive | PK11007 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53-mutated breast cancer cell lines demonstrated increased sensitivity to PK11007 compared to TP53-wild type cells in culture, regardless of Esr1 and Erbb2 (Her2) status (J Clin Oncol 35, 2017 (suppl; abstr e14099)). | detail... |
| TP53 wild-type | liposarcoma | predicted - sensitive | ALRN-6924 | Case Reports/Case Series | Actionable | In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with liposarcoma (PMID: 34301750; NCT02264613). | 34301750 |
| TP53 wild-type | colorectal cancer | predicted - sensitive | ALRN-6924 | Case Reports/Case Series | Actionable | In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with colorectal cancer (PMID: 34301750; NCT02264613). | 34301750 |
| TP53 wild-type | Merkel cell carcinoma | predicted - sensitive | ALRN-6924 | Case Reports/Case Series | Actionable | In a Phase I trial, ALRN-6924 treatment in a patient with Merkel cell carcinoma resulted in a complete response (PMID: 34301750; NCT02264613). | 34301750 |
| TP53 wild-type | peripheral T-cell lymphoma | predicted - sensitive | ALRN-6924 | Case Reports/Case Series | Actionable | In a Phase I trial, ALRN-6924 treatment in a patient with peripheral T-cell lymphoma resulted in a complete response (PMID: 34301750; NCT02264613). | 34301750 |
| TP53 wild-type | lymphoma | predicted - sensitive | ALRN-6924 | Phase I | Actionable | In a Phase I trial, treatment with ALRN-6924 in patients with advanced solid tumors and lymphomas resulted in a disease control rate of 59% (24/41), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 20 patients demonstrating stable disease (PMID: 34301750; NCT02264613). | 34301750 |
| TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | ALRN-6924 | Phase I | Actionable | In a Phase I trial, treatment with ALRN-6924 in patients with advanced solid tumors and lymphomas resulted in a disease control rate of 59% (24/41), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 20 patients demonstrating stable disease (PMID: 34301750; NCT02264613). | 34301750 |
| BRAF V600E TP53 Q192K | colon cancer | predicted - sensitive | Panitumumab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 28514312). | 28514312 |
| TP53 wild-type | thyroid gland papillary carcinoma | sensitive | APG-115 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a TP53 wild-type dedifferentiated papillary thyroid carcinoma cell line treated with APG-115 demonstrated decreased cell viability and induction of cell cycle arrest and apoptosis in culture, and tumor growth suppression and tumor regression in xenograft models (PMID: 28498808). | 28498808 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | GDC-0425 + Gemcitabine | Phase I | Actionable | In a Phase I trial, treatment with GDC-0425 followed by Gemzar (gemcitabine) resulted in a partial response in a patient with triple-receptor negative breast cancer harboring a TP53 mutation (PMID: 27815358). | 27815358 |
| TP53 del | colorectal cancer | predicted - sensitive | Doxorubicin + Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-null colorectal cancer cells in culture (PMID: 26826118). | 26826118 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Doxorubicin + Seliciclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-mutant triple-receptor negative breast cancer cell lines in culture, and inhibited tumor growth, prolonged survival in cell line xenograft models (PMID: 26826118). | 26826118 |
| PTEN loss TP53 loss | prostate cancer | sensitive | Capivasertib | Preclinical | Actionable | In a preclinical study, treatment with Truqap (capivasertib) improved overall survival and progression-free survival in mouse models of prostate cancer with inactivated PTEN and TP53 (PMID: 26910118). | 26910118 |
| TP53 del | ovarian clear cell carcinoma | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in Tp53-independent increase of Cdkn1a expression and apoptosis of ovarian clear cell carcinoma cells harboring TP53 deletion in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 mutant | ovarian serous carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment decreased mutant Tp53 level, resulted in apoptosis of ovarian serous carcinoma cells harboring TP53 mutations in culture (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 wild-type | endometrioid ovary carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment increased Tp53 and Cdkn1a protein levels, resulted in growth inhibition of TP53 wild-type endometrioid ovary carcinoma cells in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 positive | breast cancer | sensitive | Serdemetan | Phase I | Actionable | In a Phase I trial, Serdemetan (JNJ-26854165) treatment induced a 102% increase of Tp53 expression in tumor tissue, resulted in partial response in a patient with breast cancer (PMID: 21831953). | 21831953 |
| TP53 positive | Advanced Solid Tumor | sensitive | Serdemetan | Phase I | Actionable | In a Phase I trial, Serdemetan (JNJ-26854165) treatment increased Tp53 expression in tumor and surrogate tissue, resulted in partial response in 1.8% (1/57) and stable disease in 38.6% (22/57) of patients with advanced solid tumors (PMID: 21831953). | 21831953 |
| TP53 wild-type | Advanced Solid Tumor | unknown | MK-8242 | Phase I | Actionable | In a Phase I trial, MK-8242 demonstrated safety and some preliminary clinical activity in patients with TP53 wild-type advanced solid tumors, particularly those with liposarcoma (LPS), with an overall response rate (ORR) of 6.4% (3/41; all partial responses), all in patients with LPS (ORR in LPS 11.1% (3/27)), and 75.6% (31/41) of patients achieving stable disease (PMID: 28240971). | 28240971 |
| TP53 wild-type | liposarcoma | predicted - sensitive | MK-8242 | Phase I | Actionable | In a Phase I trial, MK-8242 demonstrated safety and some preliminary clinical activity in patients with advanced solid tumors, particularly those with TP53 wild-type liposarcoma (LPS), with an overall response rate (ORR) of 6.4% (3/41; all partial responses), all in patients with LPS (ORR in LPS 11.1% (3/27)), and a median progression-free survival in LPS of 237 days (PMID: 28240971). | 28240971 |
| TP53 R273W | breast cancer | resistant | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, NSC319726 did not inhibit tumor growth in xenograft models of breast cancer harboring TP53 R273W (PMID: 22624712). | 22624712 |
| TP53 wild-type | lung large cell carcinoma | resistant | NSC319726 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NSC319726 did not inhibit tumor growth in xenograft models of TP53 wild-type lung large cell carcinoma (PMID: 22624712). | 22624712 |
| TP53 R175H | breast cancer | sensitive | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726 in culture (PMID: 22624712). | 22624712 |
| TP53 R175L | lung large cell carcinoma | sensitive | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, lung large cell carcinoma cells harboring TP53 R175L demonstrated increased sensitivity to NSC319726 in culture (PMID: 22624712). | 22624712 |
| TP53 R175H | ovarian cancer | sensitive | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726-induced growth inhibition in culture and in cell line xenograft models (PMID: 22624712). | 22624712 |
| TP53 wild-type | melanoma | sensitive | APR-246 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APR-246 inhibited growth of TP53 wild-type melanoma cells in 3D culture and in cell line xenograft models (PMID: 21239882). | 21239882 |
| TP53 wild-type | colorectal cancer | predicted - sensitive | MK-8745 | Preclinical - Cell culture | Actionable | In a preclinical study, MK-8745 treatment resulted in apoptosis in Tp53 wild-type colorectal cancer cells in culture (PMID: 22293494). | 22293494 |
| TP53 R175H | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring TP53 R175H demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). | 24504419 |
| TP53 S241F | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring TP53 S241F demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). | 24504419 |
| PIK3CA H1047R TP53 S90fs | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring PIK3CA H1047R and TP53 S90fs*33 demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). | 24504419 |
| ALK rearrange RB1 C706F TP53 loss | lung small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). | 28285684 |
| TP53 loss | colorectal cancer | sensitive | PHA-680632 + Radiotherapy | Preclinical - Pdx | Actionable | In a preclinical study, PHA-680632 synergized with radiotherapy to decrease tumor growth in Pdx models deficient in Tp53 (PMID: 18026198). | 18026198 |
| TP53 wild-type | salivary gland adenoid cystic carcinoma | predicted - sensitive | SAR405838 | Preclinical - Pdx | Actionable | In a preclinical study, treatment with SAR405838 (MI-773) resulted in activation of Mdm2 and Tp53 in patient-derived salivary gland adenoid cystic carcinoma (ACC) cells in culture, and led to induction of apoptosis and tumor regression in ACC patient-derived xenograft (PDX) models with wild-type TP53 (PMID: 26936915). | 26936915 |
| TP53 loss | colorectal cancer | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD6738 increased sensitivity to radiotherapy in colorectal cancer xenograft models harboring a loss of TP53, resulting in a greater delay of tumor growth compared to radiation alone and an improved survival compared to control or either agent alone (PMID: 28062704). | 28062704 |
| TP53 mutant | pharynx squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a pharynx squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 mutant | tongue squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a tongue squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 wild-type | lung carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a lung carcinoma cell line harboring wild-type TP53 in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Siremadlin | Phase I | Actionable | In a Phase I trial, Siremadlin (HDM201) treatment demonstrated safety and resulted in an overall response rate (ORR) of 3.5% (4/115; all partial responses) and disease control rate (DCR) of 36.5% in patients with TP53 wild-type advanced solid tumors, and at the recommended dose for expansion (120 mg), resulted in an ORR of 10.5% (3/29) and DCR of 44.8% in all patients, and a DCR of 83.3% (10/12) in patients with liposarcoma (PMID: 34862243; NCT02143635). | 34862243 |
| TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Siremadlin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, HDM201 treatment resulted in tumor regression in various cell line xenograft models of Tp53 wild-type tumors (Cancer Res 2016;76(14 Suppl):Abstract nr 4855). | detail... |
| BRAF mut TP53 mut | colorectal cancer | sensitive | Alpelisib + Dabrafenib + Erlotinib + Navitoclax | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
| BRAF mut TP53 wild-type | colorectal cancer | sensitive | CGM097 + Dabrafenib + Navitoclax + PF-04217903 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
| PTEN mut TP53 mut | glioblastoma | sensitive | Navitoclax + ONC201 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of ONC201 (TIC10) and Navitoclax (ABT-263) increased apoptosis and worked synergistically to inhibit proliferation of a glioblastoma cell line harboring mutations in PTEN and TP53 in culture (PMID: 26474387). | 26474387 |
| TP53 P278R | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 P278R in culture (PMID: 27179933). | 27179933 |
| TP53 Y163H | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 Y163H in culture (PMID: 27179933). | 27179933 |
| TP53 L111Q | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 L111Q in culture (PMID: 27179933). | 27179933 |
| TP53 C238F | fallopian tube cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived fallopian tube cancer cells harboring TP53 C238F in culture (PMID: 27179933). | 27179933 |
| TP53 C135Y | peritoneum cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived peritoneum cancer cells harboring TP53 C135Y in culture (PMID: 27179933). | 27179933 |
| TP53 P151H | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 P151H in culture (PMID: 27179933). | 27179933 |
| TP53 R280K | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically in culture, resulting in reduced cell viability in patient derived ovarian cancer cells harboring TP53 R280K (PMID: 27179933). | 27179933 |
| TP53 wild-type | breast cancer | predicted - sensitive | SAR405838 | Preclinical - Pdx | Actionable | In a preclinical study, SAR405838 (MI-77301) induced p53 signaling and inhibited tumor growth in patient-derived xenograft models of endocrine therapy-resistant breast cancer with wild-type TP53, and induced cell-cycle arrest and inhibited growth of patient-derived endocrine therapy-resistant breast cancer cells in culture (PMID: 27765850). | 27765850 |
| TP53 wild-type | acute myeloid leukemia | sensitive | Cytarabine + RO6839921 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RO6839921 and Cytosar-U (cytarabine) combination treatment demonstrated anti-tumor activity in TP53 wild-type disseminated acute myeloid leukemia cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). | detail... |
| TP53 wild-type | acute myeloid leukemia | sensitive | RO6839921 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RO6839921 demonstrated anti-tumor activity in TP53 wild-type disseminated acute myeloid leukemia cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). | detail... |
| TP53 wild-type | fibrosarcoma | sensitive | Pegylated liposomal doxorubicin + RO6839921 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RO6839921 and Doxil combination treatment demonstrated sustained survival benefit in TP53 wild-type fibrosarcoma cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). | detail... |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a prtial response in 3 and progressive disease in 2 of 6 patients with advanced solid tumors harboring TP53 mutations (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a retrospective analysis of a Phase I trial, Adavosertib (MK-1775) combined with a chemotherapy resulted in a 21% (4/19) response rate in advanced solid tumor patients harboring a TP53 mutation and in those without a TP53 mutation, a 12% (4/33) response rate was observed (PMID: 27601554; NCT00648648). | 27601554 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Carboplatin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 and Paraplatin (carboplatin) synergistically inhibited growth in TP53 mutated triple-receptor negative breast cancer cell lines in culture and in cell line xenograft models (PMID: 26494859). | 26494859 |
| TP53 R249S | hepatocellular carcinoma | sensitive | CP-31398 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 R249S in culture, and inhibited tumor growth in xenograft models (PMID: 26250460). | 26250460 |
| TP53 Y220C | hepatocellular carcinoma | sensitive | CP-31398 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture (PMID: 26250460). | 26250460 |
| TP53 loss | glioblastoma | sensitive | BLZ945 | Preclinical | Actionable | In a preclinical study, treatment with BLZ945 demonstrated some efficacy, specifically a 56% tumor reduction, in transgenic mouse models of glioblastoma with a loss of TP53 (PMID: 27199435). | 27199435 |
| TP53 wild-type | colorectal cancer | predicted - sensitive | PD-0325901 + Sapanisertib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically induced apoptosis in TP53 wild-type but not TP53 mutated colorectal cancer cell lines in culture, and demonstrated anti-tumor activity in TP53 wild-type but not TP53 mutated patient-derived xenograft models (PMID: 26272063). | 26272063 |
| BRAF V600E PTEN loss TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). | 26272063 |
| BRAF V600E PIK3CA H1047R TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell culture | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture (PMID: 26272063). | 26272063 |
| BRAF V600E PIK3CA P449T TP53 R273H | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). | 26272063 |
| TP53 positive | Advanced Solid Tumor | predicted - sensitive | p28 | Phase I | Actionable | In a Phase I trial, treatment with p28 was well-tolerated and demonstrated preliminary efficacy in patients with Tp53-positive advanced solid tumors, with complete response in 6% (1/15), partial response in 20% (3/15), and stable disease in 46% (7/15) of patients (PMID: 23449360). | 23449360 |
| TP53 R273L | lung small cell carcinoma | sensitive | APR-246 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APR-246 demonstrated efficacy in cell line xenograft models of small cell lung cancer harboring TP53 R273L (PMID: 21415220). | 21415220 |
| TP53 S241F | lung small cell carcinoma | sensitive | APR-246 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APR-246 demonstrated efficacy in xenograft models of small cell lung cancer harboring TP53 S241F (PMID: 21415220). | 21415220 |
| TP53 R273H TP53 P309S | colorectal cancer | sensitive | Cisplatin + NSC59984 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Platinol (cisplatin) and NSC59984 worked synergistically to decrease viability of a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). | 26294215 |
| TP53 R248W VHL inact mut | clear cell renal cell carcinoma | resistant | PT2399 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53 R248W was associated with resistance to PT2399 in VHL-defective clear cell renal cell carcinoma cell lines in culture (PMID: 27595393). | 27595393 |
| TP53 R273H TP53 P309S | colorectal cancer | sensitive | NSC59984 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with NSC59984 induced Tp53 pathway signaling, degradation of mutant Tp53, and cell death in a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). | 26294215 |
| TP53 R175H | colorectal cancer | sensitive | NSC59984 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with NSC59984 resulted in increased degradation of mutant Tp53 and cell death in a colorectal cancer cell line harboring TP53 R175H in culture (PMID: 26294215). | 26294215 |
| TP53 R175L | colorectal cancer | sensitive | NSC59984 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with NSC59984 resulted in increased degradation of mutant Tp53 and cell death in a colorectal cancer cell line harboring TP53 R175L in culture (PMID: 26294215). | 26294215 |
| TP53 mutant | colorectal cancer | predicted - sensitive | NSC59984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NSC59984 treatment resulted in increased Tp53 signaling and cell death in colorectal cancer cell lines harboring TP53 mutations, and inhibited tumor growth in TP53-mutant cell line colorectal cancer xenograft models (PMID: 26294215). | 26294215 |
| TP53 loss | lung cancer | resistant | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) did not enhance radiation-induced cytotoxicity in TP53-null lung cancer cells in culture and in cell line xenograft models (PMID: 26162687). | 26162687 |
| TP53 wild-type | osteosarcoma | sensitive | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) enhanced radiation-induced cytotoxicity in TP53 wild-type osteosarcoma cells in culture and in cell line xenograft models (PMID: 26162687). | 26162687 |
| TP53 wild-type | colon cancer | sensitive | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) enhanced radiation-induced cytotoxicity in TP53 wild-type colon cancer cells in culture and in cell line xenograft models (PMID: 26162687). | 26162687 |
| TP53 wild-type | breast cancer | sensitive | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) enhanced radiation-induced cytotoxicity in TP53 wild-type breast cancer cells in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | melanoma | sensitive | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) enhanced radiation-induced cytotoxicity in TP53 wild-type melanoma cells in culture and in cell line xenograft models (PMID: 26162687). | 26162687 |
| TP53 wild-type | lung cancer | sensitive | KRT-232 + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) enhanced radiation-induced cytotoxicity in TP53 wild-type lung cancer cell lines in culture and in cell line xenograft models (PMID: 26162687). | 26162687 |
| TP53 loss | lung cancer | resistant | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53-null lung cancer cells were resistant to KRT-232 (AMG 232) induced growth inhibition in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | osteosarcoma | sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type osteosarcoma cells in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | melanoma | sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type melanoma cells in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | colon cancer | sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type colon cancer cells in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | breast cancer | sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) activated Tp53 signaling, resulting in growth inhibition of TP53 wild-type breast cancer cells in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | lung cancer | sensitive | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type lung cancer cell lines in culture (PMID: 26162687). | 26162687 |
| TP53 wild-type | lung non-small cell carcinoma | sensitive | Carboplatin + KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Paraplatin (carboplatin) worked synergistically to inhibit tumor growth in a TP53 wild-type non-small cell lung cancer cell line xenograft model, with increased efficacy over either agent alone (PMID: 25567130). | 25567130 |
| TP53 wild-type | lung non-small cell carcinoma | sensitive | Cisplatin + KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Platinol (cisplatin) worked synergistically to inhibit tumor growth in a TP53 wild-type non-small cell lung cancer cell line xenograft model, with increased efficacy over either agent alone, resulting in tumor stasis (PMID: 25567130). | 25567130 |
| BRAF mut TP53 wild-type | melanoma | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). | 25567130 |
| TP53 wild-type | lung non-small cell carcinoma | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) induced activation of Tp53 target genes and inhibited growth of a non-small cell lung cancer (NSCLC) cell line with wild-type TP53 in culture and inhibited tumor growth in a TP53 wild-type NSCLC cell line xenograft model (PMID: 25567130). | 25567130 |
| TP53 wild-type | Advanced Solid Tumor | sensitive | KRT-232 | Phase I | Actionable | In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 80% (31/39) of patients with TP53 wild-type advanced solid tumors, with a median duration of 3.1 months (PMID: 31359240; NCT01723020). | 31359240 |
| TP53 wild-type | Advanced Solid Tumor | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) induced activation of Tp53 target genes and inhibited growth of several human tumor cell lines with wild-type TP53 in culture and in cell line xenograft models (PMID: 25567130). | 25567130 |
| TP53 mutant | Advanced Solid Tumor | resistant | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) did not inhibit growth of human tumor cell lines harboring TP53 mutations in culture (PMID: 25567130). | 25567130 |
| TP53 V173M | acute myeloid leukemia | predicted - sensitive | APR-246 | Case Reports/Case Series | Actionable | In a Phase I trial, APR-246 demonstrated safety and preliminary clinical activity in patients with hematological cancers, including an acute myeloid leukemia patient harboring TP53 V173M that achieved a decrease in bone marrow blast percentage from 46% to 26% (PMID: 22965953). | 22965953 |
| TP53 wild-type | colon cancer | sensitive | Trifluridine | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Trifluridine (FTD) resulted in Tp53-dependent cell-cycle arrest and decreased expression of CyclinB1 and Cdk1 in a Tp53-proficient colon cancer cancer cell line in culture (PMID: 25700705). | 25700705 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody, an unspecified Erbb3 (Her3) antibody, and an unspecified Igf-1r antibody resulted in potent inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Igf-1r antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Erbb3 (Her3) antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | resistant | unspecified EGFR antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of two unspecified EGFR antibodies targeting nonoverlapping epitopes of Egfr did not inhibit proliferation of Tp53 mutated hypopharyngeal carcinoma cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | glioblastoma | sensitive | Adavosertib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Adavosertib (MK-1775) decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). | 27196784 |
| TP53 D259Y | melanoma | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of human melanoma cells TP53 D259Y in culture (PMID: 26343583). | 26343583 |
| TP53 D259Y | melanoma | sensitive | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring TP53 D259Y in culture (PMID: 26343583). | 26343583 |
| TP53 D259Y | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring TP53 D259Y in culture (PMID: 26343583). | 26343583 |
| TP53 del | ovarian cancer | sensitive | Etoposide + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis and decrease growth of ovarian cancer cells with TP53 deletion in culture (PMID: 25964101). | 25964101 |
| TP53 del | ovarian cancer | sensitive | Cisplatin + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis and decrease growth of ovarian cancer cells with TP53 deletion in culture (PMID: 25964101). | 25964101 |
| TP53 del | ovarian cancer | no benefit | Nutlin-3a | Preclinical | Actionable | In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with deletion of TP53 in culture (PMID: 25964101). | 25964101 |
| TP53 inact mut | ovarian cancer | sensitive | Cisplatin + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). | 25964101 |
| TP53 mutant | ovarian cancer | sensitive | Etoposide + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). | 25964101 |
| TP53 mutant | ovarian cancer | no benefit | Nutlin-3a | Preclinical | Actionable | In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with TP53 mutations in culture (PMID: 25964101). | 25964101 |
| TP53 R280K | triple-receptor negative breast cancer | sensitive | YW3-56 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, YW3-56 inhibited proliferation of a human triple-negative breast cancer (TNBC) cell line harboring TP53 R280K in culture and inhibited tumor growth in TP53 R280K-mutant TNBC cell line xenograft models (PMID: 25612620). | 25612620 |
| TP53 loss | colorectal cancer | sensitive | Prodigiosin | Preclinical | Actionable | In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 loss in culture (PMID: 26759239). | 26759239 |
| TP53 mutant | colorectal cancer | sensitive | Prodigiosin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 26759239). | 26759239 |
| TP53 wild-type | colorectal cancer | sensitive | Prodigiosin | Preclinical | Actionable | In a preclinical study, Prodigiosin inhibited self-renewal of Tp53 wild-type colorectal cancer cell lines in culture (PMID: 26759239). | 26759239 |
| TP53 wild-type | Advanced Solid Tumor | sensitive | CTX-1 + Nutlin-3a | Preclinical | Actionable | In a preclinical study, CTX-1 and Nutlin-3 worked cooperatively to induce cell death in several TP53 wild-type human tumor cell lines in culture (PMID: 26883273). | 26883273 |
| TP53 wild-type | acute myeloid leukemia | sensitive | CTX-1 + Nutlin-3a | Preclinical | Actionable | In a preclinical study, the combination of CTX-1 and Nutlin-3 resulting in improved survival time in mouse models of acute myeloid leukemia using TP53 wild-type primary human acute myeloid leukemia cells (PMID: 26883273). | 26883273 |
| TP53 wild-type | acute myeloid leukemia | sensitive | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 improved survival time in mouse models of acute myeloid leukemia using TP53 wild-type primary human acute myeloid leukemia cells (PMID: 26883273). | 26883273 |
| TP53 mutant | Advanced Solid Tumor | sensitive | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 induced increased Tp53 protein levels and cell death in human tumor cell lines with mutant Tp53 in culture (PMID: 26883273). | 26883273 |
| TP53 loss | Advanced Solid Tumor | decreased response | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 induced cell death in TP53-deficient human tumor cell lines in culture, but had a greater effect on cell lines with wild-type TP53 compared to isogenic cell lines with TP53 loss (PMID: 26883273). | 26883273 |
| TP53 wild-type | Advanced Solid Tumor | sensitive | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 induced cell death in several solid tumor cell lines with wild-type TP53 in culture (PMID: 26883273). | 26883273 |
| TP53 inact mut | chronic lymphocytic leukemia | sensitive | Ceralasertib + Ibrutinib | Preclinical | Actionable | In a preclinical study, AZD6738 sensitized TP53-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). | 26563132 |
| TP53 inact mut | chronic lymphocytic leukemia | predicted - sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 induced cell death in TP53-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). | 26563132 |
| TP53 wild-type | neuroblastoma | predicted - sensitive | Doxorubicin + GSK2830371 | Preclinical | Actionable | In a preclinical study, GSK2830371 and Adriamycin (doxorubicin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). | 25658463 |
| TP53 wild-type | neuroblastoma | predicted - sensitive | Carboplatin + GSK2830371 | Preclinical | Actionable | In a preclinical study, GSK2830371 and Paraplatin (carboplatin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). | 25658463 |
| TP53 mutant | neuroblastoma | resistant | GSK2830371 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutations were resistant to GSK2830371 induced growth inhibition in culture (PMID: 25658463). | 25658463 |
| TP53 wild-type | neuroblastoma | predicted - sensitive | GSK2830371 | Preclinical | Actionable | In a preclinical study, GSK2830371 inhibited proliferation of neuroblastoma cell lines carrying wild-type TP53 in culture (PMID: 25658463). | 25658463 |
| TP53 mutant | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical | Actionable | In a preclinical study, ovarian clear cell adenocarcinoma cell lines harboring TP53 mutations demonstrated reduced sensitivity to DS-7423 induced apoptosis in culture compared to TP53 wild-type cells (PMID: 24504419). | 24504419 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Duvelisib | Phase I | Actionable | In a Phase I trial, Copiktra (duvelisib) treatment inhibited Akt phosphorylation, resulted in complete response in 2% (1/49), partial response in 53% (26/49), and stable disease in 43% (21/49) of chronic lymphocytic leukemia patients, of which 49% (23/47) carried TP53 mutations (Blood 124 (21): 3334). | detail... |
| TP53 mutant | leukemia | decreased response | RG7112 | Phase I | Actionable | In a Phase I clinical trial, the majority of 19 leukemia patients with identified TP53 mutations did not demonstrate response to treatment with RG7112, with 2 acute myeloid leukemia patients harboring TP53 mutations showing clinical activity, but not improvement, and 1 sCLL/CLL patient achieving stable disease (PMID: 26459177). | 26459177 |
| TP53 P223L TP53 V274F | prostate cancer | resistant | Ganetespib | Preclinical | Actionable | In a preclinical study, Ganetespib inhibited growth of human prostate cancer cells harboring TP53 P223L and V274F in culture (PMID: 26009011). | 26009011 |
| TP53 S241F | ovarian cancer | sensitive | Ganetespib | Preclinical | Actionable | In a preclinical study, Ganetespib inhibited growth of human ovarian cancer cells harboring TP53 S241F in culture (PMID: 26009011). | 26009011 |
| TP53 R175H | breast cancer | sensitive | Ganetespib | Preclinical - Cell culture | Actionable | In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R175H in culture (PMID: 26009011). | 26009011 |
| TP53 L194F | breast cancer | sensitive | Ganetespib | Preclinical - Cell culture | Actionable | In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 L194F in culture (PMID: 26009011). | 26009011 |
| TP53 R280K | breast cancer | sensitive | Ganetespib | Preclinical | Actionable | In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R280K in culture (PMID: 26009011). | 26009011 |
| TP53 L194F | breast cancer | sensitive | Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zolinza (vorinostat) inhibited tumor growth in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). | 26009011 |
| TP53 L194F | breast cancer | sensitive | Tanespimycin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Tanespimycin (17-AAG) inhibited tumor growth in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). | 26009011 |
| TP53 L194F | breast cancer | sensitive | Tanespimycin + Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Tanespimycin (17-AAG) and Zolinza (vorinostat) were synergistic towards tumor growth inhibition in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). | 26009011 |
| TP53 R175H | Advanced Solid Tumor | sensitive | Alvespimycin + Vorinostat | Preclinical | Actionable | In a preclinical study, Alvespimycin (17-DMAG) and Zolinza (vorinostat) extended survival by 59% in mice with tumors expressing Tp53 R172H (which corresponds to R175H in the human Tp53 protein) (PMID: 26009011). | 26009011 |
| TP53 R248Q | Advanced Solid Tumor | sensitive | Ganetespib | Preclinical | Actionable | In a preclinical study, Ganetespib extended survival by 48% in mice with tumors expressing TP53 R248Q (PMID: 26009011). | 26009011 |
| TP53 mutant | sarcoma | sensitive | Pazopanib | Clinical Study - Cohort | Actionable | In a retrospective analysis, advanced sarcoma patients with TP53 mutations displayed improved progression-free survival (208 vs 136 days, p=0.036) relative to patients with wild-type TP53 when treated with Votrient (pazopanib) (PMID: 26646755). | 26646755 |
| ALK wild-type TP53 wild-type | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). | 26438783 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 mut | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 P177T | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 C176F | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). | 26438783 |
| ALK mut TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 H168R | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). | 26438783 |
| ALK act mut TP53 wild-type | neuroblastoma | predicted - sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). | 26438783 |
| ALK F1245C TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx | Actionable | In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). | 26438783 |
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). | 26438783 |
| TP53 loss | osteosarcoma | decreased response | CPUY201112 | Preclinical | Actionable | In a preclinical study, an osteosarcoma cell line lacking TP53 demonstrated a decreased response to CPUY201112 in culture, when compared to osteosarcoma cells with wild-type TP53 (PMID: 26743233). | 26743233 |
| TP53 wild-type | osteosarcoma | sensitive | CPUY201112 | Preclinical | Actionable | In a preclinical study, CPUY201112 reduced viability and induced apoptosis in an osteosarcoma cell line with wild-type TP53 in culture, and had a limited effect on an osteosarcoma cell line lacking TP53 (PMID: 26743233). | 26743233 |
| TP53 loss | colon cancer | decreased response | CPUY201112 | Preclinical | Actionable | In a preclinical study, colon cancer cells lacking TP53 had a decreased response to CPUY201112 in culture, when compared to colon cancer cells with wild-type TP53 (PMID: 26743233). | 26743233 |
| TP53 wild-type | colon cancer | sensitive | CPUY201112 | Preclinical | Actionable | In a preclinical study, CPUY201112 reduced viability and induced apoptosis in a colon cancer cell line with wild-type TP53 in culture, and had a limited effect on a colon cancer cell line lacking TP53 (PMID: 26743233). | 26743233 |
| TP53 mutant | lung non-small cell carcinoma | sensitive | CEP-8983 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). | 23428903 |
| TP53 wild-type | lung non-small cell carcinoma | sensitive | CEP-8983 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). | 23428903 |
| TP53 inact mut | ovarian cancer | sensitive | Cisplatin + LB-100 | Preclinical | Actionable | In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in a cisplatin-resistant ovarian cancer cell line harboring a TP53 inactivating mutation in culture (PMID: 25376608). | 25376608 |
| TP53 loss | ovarian cancer | sensitive | Cisplatin + LB-100 | Preclinical | Actionable | In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in cisplatin-resistant ovarian cancer cells with TP53 loss in culture and in xenograft models (PMID: 25376608). | 25376608 |
| RB1 wild-type TP53 wild-type | mantle cell lymphoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 mut | mantle cell lymphoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | melanoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of melanoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 mut | osteosarcoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of osteosarcoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
| RB1 mut TP53 mut | prostate carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of prostate carcinoma cell lines harboring Tp53 and Rb1 mutations in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 mut TP53 mut | cervical cancer | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of cervical carcinoma cell lines harboring Tp53 and Rb1 mutations (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | lung carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of lung carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 mut | colon carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | colon carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 wild-type | breast carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). | 17121911 |
| RB1 wild-type TP53 mut | breast carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
| RB1 mut TP53 mut | breast carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring TP53 and RB1 mutations in culture (PMID: 17121911). | 17121911 |
| TP53 loss | ovarian cancer | no benefit | ReACp53 | Preclinical | Actionable | In a preclincial study, ReACp53 did not induce cell death in ovarian cancer cells with loss of TP53 in culture (PMID: 26748848). | 26748848 |
| TP53 wild-type | colon carcinoma | sensitive | MPI-0479605 | Preclinical | Actionable | In a preclinical study the TTK (MPS1) inhibitor, MPI-0479605, inhibited cell cycle progression of colon carcinoma cells deficient for Tp53 with equivalent efficacy to cells with wild-type Tp53 (PMID: 21980130). | 21980130 |
| TP53 loss | colon carcinoma | sensitive | MPI-0479605 | Preclinical | Actionable | In a preclinical study the TTK (MPS1) inhibitor, MPI-0479605, inhibited cell cycle progression of colon carcinoma cells deficient for Tp53 with equivalent efficacy to cells with wild-type Tp53 (PMID: 21980130). | 21980130 |
| TP53 Y163C | lung small cell carcinoma | sensitive | APR-246 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of small lung cancer cells harboring TP53 Y163C in culture (PMID: 26086967). | 26086967 |
| TP53 R273H | lung non-small cell carcinoma | sensitive | APR-246 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of non-small lung cancer cells harboring TP53 R273H in culture (PMID: 26086967). | 26086967 |
| TP53 R248W | lung non-small cell carcinoma | sensitive | APR-246 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of non-small lung cancer cells harboring TP53 R248W in culture (PMID: 26086967). | 26086967 |
| TP53 R248Q | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of a Platinol (cisplatin)-resistant ovarian cancer cell line harboring TP53 R248Q in culture and inhibited tumor growth in TP53 R248Q-carrying ovarian cancer cell line xenograft models (PMID: 26086967). | 26086967 |
| TP53 loss | colon carcinoma | sensitive | SP600125 | Preclinical | Actionable | In a preclinical study, SP600125 induced cell death in colon carcinoma cells deficient for p53 (PMID: 22438244). | 22438244 |
| TP53 inact mut | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of ovarian carcinoma cells harboring TP53 mutations in culture, but did not effect viability of ovarian carcinoma cells with wild-type TP53 (PMID: 26748848). | 26748848 |
| TP53 Y327L | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death in human primary ovarian carcinoma cells harboring TP53 Y327L in culture (PMID: 26748848). | 26748848 |
| TP53 Y234C | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death in human primary ovarian carcinoma cells harboring TP53 Y234C in culture (PMID: 26748848). | 26748848 |
| TP53 I195* TP53 R248Q | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of human primary ovarian carcinoma cells harboring both TP53 I195* and TP53 R248Q in culture (PMID: 26748848). | 26748848 |
| TP53 R248Q | ovarian cancer | sensitive | ReACp53 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ReACp53 rescued p53 activity and decreased viability of ovarian cancer cells harboring TP53 R248Q in culture, and induced tumor regression in patient-derived ovarian cancer xenograft models harboring TP53 R248Q (PMID: 26748848). | 26748848 |
| TP53 R175H | head and neck cancer | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of head and neck carcinoma cells harboring TP53 R175H in culture (PMID: 26748848). | 26748848 |
| TP53 R175H | Advanced Solid Tumor | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, treatment with ReACp53 induced cell death in primary human uterine fibroblasts expressing TP53 R175H in culture (PMID: 26748848). | 26748848 |
| TP53 mutant | colorectal cancer | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | sarcoma | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | Advanced Solid Tumor | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) improved progression-free survival and overall survival in advanced solid tumor patients harboring TP53 hotspot mutations, and resulted in an increased stable disease rate of 45% (5/11), compared to a stable disease rate of 16% (4/25) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 R158G | lung non-small cell carcinoma | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring TP53 R158G in culture (PMID: 21325073, PMID: 23980093). | 21325073 23980093 |
| TP53 mutant | neuroblastoma | resistant | MI-63 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to MI-63 mediated growth inhibition (PMID: 21725357). | 21725357 |
| TP53 mutant | neuroblastoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to nutlin-3 mediated growth inhibition (PMID: 21725357). | 21725357 |
| PTEN mut TP53 mut | skin cancer | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, a skin cancer cell line harboring mutations in PTEN and TP53 demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). | 25261369 |
| TP53 inact mut | lung small cell carcinoma | sensitive | APR-246 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APR-246 induced apoptosis in small-cell lung cancer (SCLC) cell lines and decreased tumor growth in SCLC cell line xenograft models harboring Tp53 inactivating mutations (PMID: 21415220). | 21415220 |
| TP53 wild-type | colon cancer | sensitive | SAR405838 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR405838 inhibited growth of TP53 wild-type colon cancer cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). | 25145672 |
| TP53 wild-type | prostate cancer | sensitive | SAR405838 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR405838 inhibited growth of TP53 wild-type prostate cancer cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). | 25145672 |
| TP53 wild-type | acute leukemia | sensitive | SAR405838 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR405838 inhibited growth of TP53 wild-type acute leukemia cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). | 25145672 |
| BRAF mut TP53 wild-type | melanoma | sensitive | CGM097 + Encorafenib | Preclinical | Actionable | In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). | detail... |
| TP53 mutant | head and neck squamous cell carcinoma | sensitive | AZD7762 + Cisplatin | Preclinical | Actionable | In a preclinical study, the treatment of a head and neck squamous cell carcinoma cell line with mutant TP53 (C176F and A161S) with AZD7762, a pan Chk1/2 inhibitor, sensitizes the cells to Platinol (cisplatin) (PMID: 23839309). | 23839309 |
| TP53 mutant | glioblastoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and radiation therapy synergized to inhibit tumor growth in a human glioblastoma multiforme cell line xenograft model harboring mutant TP53 (PMID: 21992793). | 21992793 |
| TP53 wild-type | medulloblastoma | sensitive | JQ1 | Preclinical | Actionable | In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). | 24231268 |
| TP53 mutant | medulloblastoma | decreased response | JQ1 | Preclinical | Actionable | In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). | 24231268 |
| TP53 wild-type | colon cancer | sensitive | Adavosertib + PF-00477736 | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775), in combination with the Chk1 inhibitor, PF-00477736, showed efficacy in various human cancer cell lines (breast, ovarian, colon, prostate), independently of p53 status (PMID: 22713237). | 22713237 |
| TP53 loss | Advanced Solid Tumor | sensitive | Adavosertib | Preclinical | Actionable | In a preclinical study, tumor cell lines carrying deficient TP53 were sensitized to DNA-damaging agents upon Adavosertib (MK-1775) administration (PMID: 19887545). | 19887545 |
| TP53 inact mut | breast cancer | sensitive | AMG 900 | Preclinical | Actionable | In a preclinical study, breast cancer cell lines with TP53 loss of function mutations had more pronounced apoptosis after treatment with AMG 900 in culture (PMID: 24091768). | 24091768 |
| TP53 negative | breast cancer | sensitive | Bevacizumab + Docetaxel + Doxorubicin | Phase I | Actionable | In a pilot trial, TP53-negative breast cancer patients demonstrated increased survival following treatment with Avastin (bevacizumab) in combination with chemotherapy agents, Adriamycin (doxorubicin) and Taxotere (docetaxel), compared to patients with TP53-positive tumors (PMID: 21399868). | 21399868 |
| TP53 P72R | lung non-small cell carcinoma | sensitive | Cisplatin + Irinotecan | Phase I | Actionable | In phase I clinical studies, NSCLC patients with TP53 P72R mutations had a longer progression-free survival than wild-type TP53 patients, after combined treatment with Camptosar (irinotecan) and Platinol (cisplatin) (PMID: 18618574). | 18618574 |
| TP53 P177T | osteosarcoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, TP53 P177T resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). | 21643018 |
| TP53 E258Q | osteosarcoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, TP53 E258Q resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). | 21643018 |
| TP53 I232S | osteosarcoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, TP53 I232S resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). | 21643018 |
| TP53 R280M | osteosarcoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, TP53 R280M resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). | 21643018 |
| TP53 inact mut | breast cancer | sensitive | Adavosertib + Radiotherapy | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775) increased the efficacy of radiation in breast cancer cells with defective TP53 in culture (PMID: 21799033). | 21799033 |
| TP53 P72R | sarcoma | sensitive | Doxorubicin + Ifosfamide | Phase I | Actionable | In a Phase I clinical trial, sarcoma patients harboring TP53 P72R mutations had longer progression-free survival after treatment with Cyfos (ifosfamide) and Adriamycin (doxorubicin) (PMID: 23165797). | 23165797 |
| TP53 wild-type | sarcoma | sensitive | Adavosertib + Gemcitabine | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and Gemzar (gemcitabine) induced cell death in a variety of sarcoma cell lines and inhibited tumor growth in a patient-derived sarcoma xenograft model, independent of TP53 mutational status (PMID: 23520471). | 23520471 |
| TP53 wild-type | Advanced Solid Tumor | decreased response | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I study, patients with advanced solid tumor harboring TP53 mutations had increased progression-free survival and overall survival than TP53 wild-type patients after treatment with Votrient (pazopanib) in combination with Zolinza (vorinostat) (J Clin Oncol 32:5s, 2014 (suppl; abstr 2576)). | detail... |
| TP53 P72R TP53 Y220C | breast cancer | no benefit | Cyclophosphamide + Epirubicin | Phase I | Actionable | In a Phase I clinical trial, a breast cancer patient carrying TP53 P72R and Y220C mutations demonstrated incomplete response to treatment with an Ellence (epirubicin)-Cytoxan (cyclophosphamide) combination regimen (PMID: 17388661). | 17388661 |
| TP53 wild-type | ovarian cancer | no benefit | p53-SLP vaccine | Phase II | Actionable | In a Phase II trial, p53-SLP vaccine was demonstrated to be safe, well tolerated and to induce p53-specific T-cell responses in ovarian cancer patients; however clinical impact was lacking (PMID: 19621448, PMID: 21328579). | 21328579 19621448 |
| TP53 positive | Advanced Solid Tumor | sensitive | MVAp53 | Phase I | Actionable | In a phase I study, Ankara (MVAp53) demonstrated safety and efficacy in patients with metastatic colon, gastric and pancreas cancer stained positive for p53 (J Clin Oncol 31, 2013 (suppl; abstr 3089)). | detail... |
| TP53 loss | pancreatic cancer | sensitive | Adavosertib + Gemcitabine | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and Gemzar (gemcitabine) inhibited Wee1 expression, Cdc2 phosphorylation, and tumor growth in several patient-derived xenograft models of pancreatic cancer harboring TP53 mutations (PMID: 21389100). | 21389100 |
| TP53 P72R | breast cancer | unknown | Epirubicin | Phase I | Actionable | In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations, who were also hormone receptor negative, demonstrated a favorable response to Ellence (epirubicin) in combination with other chemotherapeutic agents (PMID: 22903472). | 22903472 |
| TP53 loss | colorectal cancer | predicted - sensitive | Ad5CMV-p53 gene | Preclinical | Actionable | In a preclinical study, Ad5CMV-p53 gene therapy suppressed growth of allograft colorectal cancer in rat models (PMID: 15608394). | 15608394 |
| TP53 wild-type | ovarian cancer | predicted - sensitive | Ad.p53-DC vaccine | Phase I | Actionable | In Phase I and Phase II clinical trials, various forms of p53 gene therapy (such as adenoviral-p53) have been shown to be generally safe and have demonstrated clinical efficacy in patients with ovarian cancer (PMID: 12082455; PMID: 19621448; PMID: 21927947; PMID: 15297186; PMID: 12082456). | 15297186 21927947 19621448 12082455 12082456 |
| TP53 inact mut | ovarian cancer | sensitive | Adavosertib + Carboplatin + Paclitaxel | Phase II | Actionable | In a Phase II trial, treatment with Adavosertib (MK-1775) plus Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in an improved progression-free survival by enhanced RECIST of 7.9 mo vs. 7.3 mo with placebo plus chemotherapy, and complete response in 11/9% (7/59) vs. 8.9% (5/62), partial response in 62.7% (37/59) vs. 61.3% (38/62), and stable disease in 5.1% (3/59) vs. 4.8% (3/62) of patients with platinum-sensitive ovarian cancer harboring an inactivating TP53 mutation (PMID: 32611648; NCT01357161). | 32611648 |
| TP53 mutant | colorectal cancer | sensitive | PD0166285 | Preclinical | Actionable | In a preclinical study, PD0166285 sensitizes colorectal cancer cells with TP53 mutation to radiation induced cell death (PMID: 11719452). | 11719452 |
| TP53 mutant | Advanced Solid Tumor | sensitive | Bevacizumab | Clinical Study - Cohort | Actionable | In a retrospective study, Avastin (bevacizumab) treatment was associated with increased progression-free survival in cancer patients carrying TP53 mutations (PMID: 23670029). | 23670029 |
| TP53 mutant | mantle cell lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with mantle cell lymphoma who are treated with conventional therapy, including transplant (NCCN.org). | detail... |
| TP53 mutant | B-cell acute lymphoblastic leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | not applicable | N/A | Guideline | Prognostic | Loss of TP53 is associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). | detail... |
| TP53 mutant | acute myeloid leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). | detail... |
| TP53 mutant | medulloblastoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with aggressive disease in patients with SHH-activated medulloblastoma (NCCN.org). | detail... |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with inferior leukemia-free survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | TP53 mutations except P47S and P72R are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| TP53 mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing breast cancer (NCCN.org). | detail... |
| TP53 mutant | nephroblastoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing Wilms tumor (nephroblastoma) (NCCN.org). | detail... |
| TP53 mutant | osteosarcoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing osteosarcoma (NCCN.org). | detail... |
CKB BOOST