A research team from the University of California San Diego identified biomarkers that may predict the response of metastatic colorectal cancer (mCRC) patients to chemotherapy. The results entitled “ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer”, and published in PLOS ONE, may help physicians make more informed treatment decisions for patients.
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. New drugs have improved the overall survival (OS) rates of patients and many survive beyond two years after diagnosis. Importantly, patients who respond to the initial therapy have longer OS. Typical treatment includes two chemotherapy drugs, 5-Fluorouracil in combination with either oxaliplatin or irinotecan but oncologists have to decide the first line of chemotherapy for each patient.
“Several large trials compared oxaliplatin and irinotecan head-to-head and concluded that the response rate is about equal. How an oncologist bases his or her treatment decision can be based on experience, comfort level prescribing and the patient’s health,” said senior author Paul Fanta. “But in reality, the two drugs are very different. For any individual patient, one might be better than the other. As an oncologist, how do I know which is better for my patient? That’s where this study comes in,” he added in a press release.
The results from this study can help oncologists to better predict the response of an individual patient to the first line chemotherapy. Researchers used commercially available test to analyze ERCC1 and TS genetic expression in 41 patients with mCRC. The team found that patients with low ERCC1 levels had longer OS (36 months) compared to patients with high ERCC1 levels (10 months). Likewise, patients with low TS levels had improved OS (36 months) when compared to patients with high TS levels (15 months).
Patients with low levels of both ERCC1 and TS responded better to oxaliplatin, suggesting that this should be the first line chemotherapy for these patients. In contrast, patients responded to irinotecan at the same rate whether they had low or high levels of these genes, giving physicians the indication of the first-choice chemotherapy for this group of patients.
Although with a modest number of patients, this study suggests that ERCC1 and TS profiling could help physicians to optimize therapy allowing some of these patients to proceed to surgical removal of metastatic tumors.
“Our study is small, retrospective and all of the patients were located at a single medical center, but it demonstrates that it’s possible to use molecular diagnostics to identify subgroups of patients more likely to respond to a given treatment,” said co-first author John Paul Shen. “Given this proof-of-principle, it’s our hope that molecular biomarkers will be included in future prospective clinical trials in metastatic colorectal cancer.”