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Gene | TP53 |
Variant | inact mut |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 inact mut indicates that this variant results in a loss of function of the Tp53 protein. However, the specific amino acid change has not been identified. |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 inact mut |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 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 | 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 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 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 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 | 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 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 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 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 |