Reference Detail

Ref Type Journal Article
PMID (27798265)
Authors Zhang L, Theodoropoulos PC, Eskiocak U, Wang W, Moon YA, Posner B, Williams NS, Wright WE, Kim SB, Nijhawan D, De Brabander JK, Shay JW
Title Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer.
Journal Science translational medicine
Vol 8
Issue 361
Date 2016 Oct 19
URL
Abstract Text Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC), and more than 90% of those mutations generate stable truncated gene products. We describe a chemical screen using normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein. With this screen, we identified a small molecule, TASIN-1 (truncated APC selective inhibitor-1), that specifically kills cells with APC truncations but spares normal and cancer cells with wild-type APC. TASIN-1 exerts its cytotoxic effects through inhibition of cholesterol biosynthesis. In vivo administration of TASIN-1 inhibits tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity. TASIN-1 represents a potential therapeutic strategy for prevention and intervention in CRC with mutant APC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
TASIN-1 TASIN-1 8 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
TASIN-1 TASIN-1 is a small molecule that selectively inhibits growth of cancer cells expressing truncated APC through inhibition of cholesterol biosynthesis (PMID: 27798265).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
APC G1416* colorectal cancer sensitive TASIN-1 Preclinical - Cell culture Actionable In a preclinical study, TASIN-1 inhibited survival of colorectal cancer cell lines harboring APC G11416* in culture (PMID: 27798265). 27798265
APC Q1338* colorectal cancer sensitive TASIN-1 Preclinical - Cell culture Actionable In a preclinical study, TASIN-1 inhibited survival of colorectal cancer cell lines harboring APC Q1338* in culture (PMID: 27798265). 27798265
APC E1309* colorectal cancer sensitive TASIN-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TASIN-1 efficiently inhibited survival of colorectal cancer cells harboring APC E1309* in culture and in cell line xenograft models (PMID: 27798265). 27798265
APC E853* APC K1555* colorectal cancer sensitive TASIN-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TASIN-1 efficiently inhibited survival of colorectal cancer cells harboring APC E853* and K1555* in culture and in cell line xenograft models (PMID: 27798265). 27798265
APC Q1131* APC Q1303* colorectal cancer sensitive TASIN-1 Preclinical - Cell culture Actionable In a preclinical study, TASIN-1 inhibited survival of colorectal cancer cells harboring APC Q1131* and Q1303* in culture (PMID: 27798265). 27798265
APC L1488* colorectal cancer sensitive TASIN-1 Preclinical - Cell culture Actionable In a preclinical study, TASIN-1 inhibited survival of colorectal cancer cells harboring APC L1488* in culture (PMID: 27798265). 27798265
APC wild-type colorectal cancer resistant TASIN-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TASIN-1 did not inhibit survival of APC wild-type colorectal cancer cells in culture or in cell line xenograft models (PMID: 27798265). 27798265
APC inact mut colorectal cancer sensitive TASIN-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TASIN-1 efficiently inhibited survival of colorectal cancer cell lines harboring APC truncation mutations in culture and in cell line xenograft models (PMID: 27798265). 27798265