RasGRP1: Potential Biomarker of Therapeutic Response in Colorectal Cancer?
Posted: Friday, September 6, 2019
According to research published in the Journal of Clinical Investigation (JCI) Insight, RasGRP1 is a potential biomarker that may be useful in predicting clinical outcome in patients with colorectal cancer undergoing anti-EGFR therapy, such as with cetuximab. “In sum, our data support RasGRP1 as a biomarker in the EGFR pathway that has potential relevance to anti-EGFR therapy to [colorectal cancer] patients,” concluded Philippe Depeille, PhD, of the University of California San Francisco, and colleagues.
Researchers mined five data platforms to analyze the effect of RasGRP1 on colorectal tumors as well as the association between its expression and predicting clinical outcomes. RasGRP1 was found to suppress colorectal tumors in patients experiencing abnormal Wnt signaling. It also inhibited the multiplication of colonic epithelial organoids, demonstrating the biomarker may affect biology.
Using patient data available from the platforms, researchers observed that the expression of RasGRP1 declined as patients experienced disease progression. In addition, a decrease in RasGRP1 expression levels was found to be a prognosticator of poor clinical outcome. Researchers also analyzed a previous clinical trial, known as CALGB 80203, and found that patients whose tumors exhibited low levels of RasGRP1 suppressor experienced significant survival benefits from undergoing combination anti-EGFR treatment and chemotherapy. Colorectal cancer spheroids became more vulnerable to anti-EGFR therapy if one or two RasGRP1 alleles were deleted, they reported.
Disclosure: The study authors’ disclosure information may be found at insight.jci.org.