Molecular Profile Detail

Profile Name TP53 wild-type
Gene Variant Detail

TP53 wild-type (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 wild-type lung cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type lung cancer cell lines in culture (PMID: 26162687). 26162687
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 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 45% (25/55), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 21 patients demonstrating stable disease (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type Merkel cell carcinoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment in a patient with Merkel cell carcinoma resulted in a complete response (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type acute myeloid leukemia sensitive CTX-1 + Nutlin-3 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 fibrosarcoma sensitive Doxil + 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 wild-type colon cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type colon cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type papillary thyroid 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 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 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 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 colorectal cancer sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with colorectal cancer (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
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
TP53 wild-type non-small cell lung 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 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 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 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 wild-type colon cancer sensitive MK-1775 + PF-00477736 Preclinical Actionable In a preclinical study, 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 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 wild-type breast cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type breast cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type osteosarcoma sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, 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 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 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 Advanced Solid Tumor sensitive HDM201 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...
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 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 melanoma sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type melanoma cells in culture (PMID: 26162687). 26162687
TP53 wild-type melanoma sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, 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 osteosarcoma sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type osteosarcoma cells in culture (PMID: 26162687). 26162687
TP53 wild-type Advanced Solid Tumor sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, 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 wild-type neuroblastoma predicted - sensitive Carboplatin + GSK2830371 Preclinical Actionable In a preclinical study, GSK283071 and Paraplatin (carboplatin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). 25658463
TP53 wild-type sarcoma sensitive MK-1775 + Gemcitabine Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of 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 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 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 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 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 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 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 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 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 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 wild-type lung carcinoma sensitive AZD6738 + 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 peripheral T-cell lymphoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment in a patient with peripheral T-cell lymphoma resulted in a complete response (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type breast cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type breast cancer cells in culture (PMID: 26162687). 26162687
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 colon cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, 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 colorectal cancer predicted - sensitive MLN0128 + PD-0325901 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
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 wild-type neuroblastoma predicted - sensitive Doxorubicin + GSK2830371 Preclinical Actionable In a preclinical study, GSK283071 and Adriamycin (doxorubicin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). 25658463
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 wild-type non-small cell lung 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 wild-type non-small cell lung carcinoma sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, 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 non-small cell lung carcinoma sensitive AMG 232 + Carboplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of 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 cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, 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 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 wild-type non-small cell lung carcinoma sensitive AMG 232 + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of 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
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
TP53 wild-type liposarcoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with liposarcoma (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type Advanced Solid Tumor sensitive CTX-1 + Nutlin-3 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 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 45% (25/55), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 21 patients demonstrating stable disease (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
Clinical Trial Phase Therapies Title Recruitment Status
NCT02842125 Phase I Ad5CMV-p53 gene + Capecitabine Safety and Efficacy of Intra-Arterial Ad-p53 in Liver Metastases of Solid Tumors Not yet recruiting
NCT03634228 Phase Ib/II Cytarabine + DS-3032b MDM2 Inhibitor DS-3032b and Low-Dose Cytarabine in Treating Participants With Newly Diagnosed Recurrent or Refractory Acute Myeloid Leukemia Recruiting
NCT02264613 Phase Ib/II ALRN-6924 Safety Study of ALRN-6924 in Patients With Advanced Solid Tumors Recruiting
NCT03107780 Phase I AMG 232 MDM2 Inhibitor AMG-232 in Treating Patients With Recurrent or Newly Diagnosed Glioblastoma Recruiting
NCT03725436 Phase I ALRN-6924 + Paclitaxel ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors Recruiting
NCT02143635 Phase I HDM201 Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt Active, not recruiting
NCT01760525 Phase I CGM097 A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors Active, not recruiting
NCT03041688 Phase I AMG 232 + Decitabine MDM2 Inhibitor AMG-232 and Decitabine in Treating Patients With Relapsed, Refractory, or Newly-Diagnosed Acute Myeloid Leukemia Recruiting
NCT01914900 Phase II Cisplatin + Docetaxel + Fluorouracil Preoperative TPF Chemotherapy in a Population of Molecularly Selected Locally Advanced Resectable Oral Cavity Squamous Cell Cancer Unknown status
NCT02909972 Phase I ALRN-6924 + Cytarabine ALRN-6924 Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome Recruiting