Hepatocellular carcinoma (HCC) and Colorectal cancer (CRC) are leading causes of cancer-related deaths worldwide. A large portion of both CRC and HCC are driven by mutations in the WNT pathway (i.e. APC or β-catenin (CTNNB1)) for which there are currently no precision therapeutics available. Using chemical libraries derived from clinical multi-kinase inhibitor (KI) scaffolds, we  identified WNTinib, a KI with exquisite selectivity in CTNNB1-mutated human and murine models, including patient samples. Multiomic and target engagement analyses, combined with rescue experiments and in vitro and in vivo efficacy studies, revealed that WNTinib is superior to clinical KIs and inhibits KIT/MAPK signaling at multiple nodes (Rialdi et al., Nature Cancer). I will additionally share how we are expanding a similar multi-omic pipeline to discover the therapeutic relevance of Oncofetal reprogramming in CRC (Mzoughi et al., Nature Genetics in press).

HOST
Prof Antonio Bertoletti
Professor
Emerging Infectious Diseases Programme
Duke-NUS Medical School

Prof David Virshup
Director
Cancer and Stem Cell Biology Programme
Duke-NUS Medical School

VENUE
Duke-NUS Medical School
Amphitheatre, Level 2

CONTACT PERSON
Ms Serene Wie (serene.wie@duke-nus.edu.sg)
Duke-NUS Research Affairs Department