Researchers Predict Which Colon Cancer Patients Will Benefit from Chemotherapy

A newly identified biomarker shows promise in predicting whether patients have a need for chemotherapy in colon cancer patients post-surgery.

In a study published in the New England Journal of Medicine, researchers noted that the protein CDX2 helps identify patients who could remain disease free up to 5 years after surgery. This discovery could also help determine the benefits of chemotherapy for stage 2 colon cancer patients.

"Because previous studies did not take into account differences between colon cancers with and without CDX2, doctors have long struggled to identify which Stage II colon cancer patients might benefit from adjuvant chemotherapy," said lead author Debashis Sahoo, PhD. "But what we've now found is that some of these patients might benefit from chemotherapy, and we now have a biomarker to tell the difference, potentially saving many lives and reducing toxicity from unnecessary treatment."

Sahoo previously developed a process to differentiate gene expression patterns in order to find genes that take part in stem cell differentiation, which is the process of stem cells that specialize into certain cell types in an organ.

"Dr. Sahoo's bioinformatics approach is extraordinarily powerful," said co-author Piero Dalerba, MD. "We used it to search for biomarkers that could help us identify which colon tumors were likely to contain high numbers of stem-like cells."

Researchers found that when the gene CDX2 is “off,” a molecular marker of cells found in colon tumors called ALCAM is always “on.”

"We reasoned that colon tumors lacking CDX2 would likely contain a higher number of stem-like cells, and would therefore be more aggressive than CDX2-positive tumors," Dalerba said.

Researchers then studied a database of more than 2000 patients with cancer gene expression who had known treatment courses and outcomes. The results of the study showed that 4% of colon cancers do not have CDX2.

When looking at a database of 466 patients who were in all different stages of colon cancer, researchers found that CDX2-negative tumors were associated with an unfavorable prognosis. There were 41% of colon cancer patients with CDX2-negative tumors who survived 5 years without the disease compared with 74% who had CDX2-positive colon tumors.

The study concluded that you can improve the survival of CDX2-negative stage 2 colon cancer patients with chemotherapy. Ninety-one percent of these patients survived 5 years when treated with chemotherapy, while 56% survived 5 years without chemotherapy.

"While promising, this study was retrospective, meaning we looked back at existing patient data,” Sahoo said. “Before they can be applied to clinical practice, these results need to be confirmed by prospective, randomized clinical trials."