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	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	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	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	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	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	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	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	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...
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	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	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	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...