Targeting Wnt in BRAF-Mutant Colorectal Cancer

Luke Dow, PhD, assistant professor of biochemistry and medicine, Weill Cornell Medicine, discusses phase I trials targeting the Wnt signaling pathway in colorectal cancer (CRC).

A phase I trial used a porcupine (PORCN) inhibitor to block the release of Wnt ligands from the cells in BRAF-mutant CRC, explains Dow. The PORCN inhibitor was combined with BRAF inhibitors and an EGFR inhibitor to block MAP kinase activation, says Dow.

There are 2 additional phase I trials that are open and actively recruiting using similar PORCN inhibitors. These are early-phase, dose-escalation trials looking at the safety rather than efficacy of the PORCN inhibitors, according to Dow. Once safety is established, Dow anticipates the PORCN inhibitors will be combined with existing therapies to target relevant pathways.