Dr Turk on Persistent Unmet Needs in Colorectal Cancer Treatment

Anita Turk, MD, discusses the unmet needs that persist in the treatment and management of gastrointestinal malignancies like colorectal cancer.

"Unfortunately, a majority of our patients don't have microsatellite instability or deficient MMR proteins in their disease, so they won't respond to immunotherapy in the same way as patients who do have those findings in their tumors. For these patients, we're largely stuck with chemotherapy," Turk explains.

Microsatellite-stable (MSS) tumors are often described as "immune cold" with a low tumor mutational burden and fewer neoantigens, making them largely unresponsive to current immune checkpoint inhibitors alone. The tumor microenvironment in MSS colorectal cancer is distinct and can actively suppress immune cell infiltration and activity. Factors like tumor-associated macrophages, TGF-β signaling, Wnt signaling, and MAPK pathway activation are implicated in creating this immune-excluded environment.

Turk adds, "And even though we've seen great advances in targeted therapy, that still only represents a very small portion of patients. We really need to understand the right combination of immune therapies—whether we add them to chemotherapy or use them by themselves—to improve long-term outcomes for this patient group, which, honestly, represents the majority of our [patients with colorectal cancer]."