For colorectal cancer caused by mutations in the RAS gene, the anticancer drug cetuximab remains the most formidable defense. Unfortunately, nearly half of the patients with metastatic colorectal cancer don’t respond to this drug option. Now, a study finds a blood biomarker can predict whether a patient will respond to cetuximab treatment, thus personalizing cancer medicine for patients with colorectal cancer.
Cetuximab (ERBITUX ™) is an antibody that inhibits the epidermal growth factor receptor (EGFR), preventing cancer cells from growing. In clinical trials, researchers showed this drug is potent against several metastatic cancers, including non-small cell lung cancer, head and neck cancer, and colorectal cancer. Even so, doctors were puzzled at why some colorectal cancer patients seemed to respond to the drug, while others didn’t. Given that the drug is expensive and has side-effects, correctly predicting patient response to the drug hugely important for treatment decisions.
"Our research discovered that the blood marker FCGR2A identifies a new group of patients that will benefit from taking cetuximab. With this finding, we believe we are now on the way to move it into the clinical setting to provide patients targeted, effective treatment," said Geoffrey Liu, investigator at the Princess Margaret Cancer Centre in Canada. The findings were obtained using archived tumor and normal tissue samples from an international clinical trial conducted 10 years ago. In total, they analyzed tissues from 572 patients.
"We need to find other ways to personalize cancer medicine for people with colorectal disease, keeping in mind that cetuximab is an expensive drug and can have side effects," said Liu. "So instead of looking at aspects in the tumour, which is where RAS
mutations show up, we looked at certain things in the blood and normal tissues that we could measure for heritable genetic variations."
The gene FCGR2A
encodes a protein that makes up part of the immunoglobulin gamma receptor, and plays an essential role in the protection of the organism against foreign antigens. Polymorphisms, or mutations, in this gene have previously been implicated in altering responses to drugs such as cetuximab.
Liu’s study adds evidence that patients who carry different mutations in the FCGR2A
gene process cetuximab differently. Specifically, they found that patients with the designated H/H version of the gene responded well to the drug, whereas patients with H/R or R/R versions had poor responses and, consequently, lower survival outcomes.
With this knowledge, the team hopes to screen metastatic colorectal cancer patients for variations in the FCGR2A
gene, and tailor cetuximab therapy to fit the patient’s genetic profile. They are now working to validate these findings in larger studies.
Additional sources: EurekAlert!