The Dutch Cancer Society (KWF Kankerbestrijding) has awarded a total of 5.5 million euro to ten Amsterdam UMC research groups for cancer research. One of the project proposals selected is entitled “Effective treatments for colon cancer peritoneal metastases” by principal investigator Dr. Maarten Bijlsma (€ 710.680). His group has identified the molecular subtype of colon cancer that metastasizes to the peritoneum, the membrane lining the abdomen. In this investigation, Dr. Bijlsma’s team will search for compounds that will exploit vulnerabilities of the subtype to identify new drugs for clinical treatment.
Nearly all solid cancers can give rise to peritoneal metastases (PM), but typically these are seen in particular colorectal, ovarian and gastric cancer. Current treatment regimens against PM include cytoreductive surgery followed by intraperitoneal application of heated chemotherapeutics, but long-term responses are disappointing. We have found that PM represent a previously identified molecular subgroup of colorectal cancer, and that this explains their metastatic capacity and, importantly, their resistance to the currently used chemotherapeutics. We have recently identified actionable vulnerabilities of this molecular subtype, and found that compounds that target this have high efficacy against proxies for PM in vitro. In the funded project, we will expand the repertoire of compounds with efficacy against PM, and test the efficacy of these candidate treatments in advanced in vivo models for PM and PM-derived organoid cultures in which the heterogeneity among patients is captured. The overarching goal is to present a set of compounds that can be further developed for clinical application and testing in trial settings.
