Molecular Profile Detail

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Profile Name TP53 Y220C
Gene Variant Detail

TP53 Y220C (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 Y220C lung non-small cell carcinoma sensitive p53 Activator 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 Y220C hepatocellular carcinoma sensitive p53 Activator 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 prostate cancer predicted - sensitive p53 Activator 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 breast cancer predicted - sensitive p53 Activator 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 p53 Activator 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 Y220C hepatocellular carcinoma sensitive p53 Activator 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 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 Y220C breast ductal carcinoma sensitive p53 Activator 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 Y220C colorectal cancer predicted - sensitive p53 Activator 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 stomach cancer predicted - sensitive p53 Activator 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...
TP53 Y220C hepatocellular carcinoma sensitive p53 Activator 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 Y220C Advanced Solid Tumor predicted - sensitive p53 Activator 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 Advanced Solid Tumor predicted - sensitive p53 Activator 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...
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04585750 Phase Ib/II PC14586 This Study Will Evaluate PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation Recruiting USA 0