Colorectal cancer is treated successfully in many patients, but it comes back in roughly 30% of cases after surgical intervention. That recurrence rate has been one of the most persistent challenges in oncology, and it is largely driven by a specific type of cell that conventional therapies struggle to eliminate. New research is pointing toward a protein that may control those cells in ways that could eventually change how the disease is treated.
A study published in Cancer Biology and Medicine focuses on a protein called BEX2 and its role in regulating colorectal cancer stem cells, the subset of tumor cells responsible for self-renewal, spread, and resistance to treatment.
What cancer stem cells do and why they are so difficult to treat
Cancer stem cells are not a majority within a tumor, but they are the most consequential. Unlike other cancer cells, they can renew themselves, generate new tumor cells, and survive the treatments that destroy the cells around them. That resilience makes them the primary driver of recurrence after surgery or chemotherapy appears to have cleared the disease.
Their behavior is governed by a set of biological pathways, and disrupting those pathways without harming healthy tissue has been one of the central problems in oncology for years. The new research suggests BEX2 may be a lever worth pulling.
How BEX2 works inside colorectal cancer cells
The study found that BEX2 functions as a regulator of cancer cell behavior by limiting what researchers describe as stemness, the set of properties that make cancer cells self-sufficient and difficult to destroy. When BEX2 levels are high, cancer cells behave in a more controlled way and respond better to treatment. When BEX2 levels are low, those same cells take on more aggressive, stem-like characteristics.
The mechanism behind this involves a molecule called MCL1, which supports cancer cell survival and is frequently overexpressed in colorectal tumors. BEX2 promotes the breakdown of MCL1, effectively marking it for destruction. That process dampens the activity of the Hedgehog signaling pathway, a growth-accelerating system closely associated with maintaining cancer stem cells in an aggressive state.
Dr. Ketan Thanki, a board-certified colorectal surgeon, described the pathway as a growth accelerator that keeps stem-like cancer cells fueled and active. Keeping it switched off, he said, could meaningfully change how the disease is treated.
What the findings could mean for patients with colorectal cancer
The research establishes a connection between low BEX2 expression and worse outcomes in colorectal cancer patients. If that relationship holds up in larger clinical studies, BEX2 could serve two purposes. First, as a biomarker that helps identify which tumors carry a higher risk of recurrence at the time of diagnosis. Second, as a therapeutic target that, when activated or restored, could reduce the population of treatment-resistant cells driving relapse.
Thanki noted that the data are promising but emphasized that clinical application remains years away. Moving from a biological finding to a validated biomarker used in treatment decisions requires a longer and more rigorous path than a single study can provide.
A shift in how colorectal cancer treatment is being approached
What makes this line of research notable is its direction. Rather than focusing primarily on shrinking tumors, it targets the mechanism that allows them to return. Tumor reduction has long been the central goal of colorectal cancer treatment, but if the cells responsible for recurrence are left intact, a patient’s chances of relapse remain significant regardless of how well the initial treatment appears to work.
Targeting cancer stem cells directly addresses that gap. BEX2, if it proves viable as both a marker and a target, could add a new layer to treatment planning that accounts not just for what is visible in the tumor at diagnosis but for what is most likely to drive the disease forward after treatment ends.
The research is early. The implications, if the findings are confirmed, could be substantial.
