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|Molecular Profile||Indication/Tumor Type||Response Type||Relevant Treatment Approaches||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|TP53 inact mut||ovarian cancer||sensitive||Adavosertib + Carboplatin + Paclitaxel||Phase I||Actionable||In a Phase I 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 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 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 inact mut||lung small cell carcinoma||sensitive||p53 Activator||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 inact mut||ovarian carcinoma||sensitive||p53 Activator||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 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 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 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||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 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 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 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|
|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||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|