Molecular Profile Detail

Profile Name TP53 inact mut
Gene Variant Detail

TP53 inact mut (loss of function)

Relevant Treatment Approaches p53 Activator p53 Gene Therapy

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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 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 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 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 cancer sensitive Cisplatin + Nutlin-3 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 + 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 chronic lymphocytic leukemia sensitive AZD6738 + 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 Adavosertib + Carboplatin + Paclitaxel Phase I Actionable In a Phase I trial, ovarian patients with TP53 deficiency had a 78.6% response rate to Adavosertib (MK-1775) in combination with carboplatin and paclitaxel (J Clin Oncol 31, 2013 (suppl; abstr 5518)). detail...
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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status
NCT03144804 Phase II Lamivudine A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer Recruiting
NCT03654716 Phase I ALRN-6924 + Cytarabine ALRN-6924 Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer Recruiting