Luke Dow, PhD, assistant professor of biochemistry and medicine, Weill Cornell Medicine, discusses the next steps for researching the Wnt pathway in colorectal cancer.

Currently, Wnt research is being guided by the clinic, explains Dow. Researchers are looking at the types of alterations seen through genomic profiling and from early-phase clinical trials to understand what is working, says Dow. From there, clinically relevant questions can be addressed.

Researchers are focused on defining, from a genetic standpoint, who would be most susceptible to Wnt-targeted therapies as well as who may show complete resistance to targeted approaches, according to Dow. Then, a patient subset likely to respond to these compounds in the clinic can be defined, concludes Dow.

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Luke Dow, PhD, discusses the next steps for researching the Wnt pathway in colorectal cancer.

Next Steps for Wnt Research in 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 

-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.

Luke Dow, PhD, discusses phase I trials targeting the Wnt signaling pathway in colorectal cancer.

Luke Dow, PhD

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