ALK and ROS1 gene rearrangements known to drive subsets of lung cancer are also present in some colorectal cancers, according to research from a University of Colorado Cancer Center study published online in Molecular Cancer Research.
These results imply that drugs used to target ALK and ROS1 in lung cancer may also have applications in this subset of colorectal cancer patients.
In the study, researchers used the technique known as fluorescence in situ hybridization (FISH) to test for the oncogenic gene rearrangements in 236 tumor samples of colorectal cancer collected from patients enrolled in a large, Australian clinical trial.
The work found one patient carrying the ALK rearrangement, confirming previous findings, and demonstrated the first finding of ROS1 as an oncogenic driver of colorectal cancer—in this case found in 2 of the 236 tumor samples.
“Even though the percentage of colorectal cancer patients with these gene rearrangements is small, the benefit to these few patients could be dramatic. It’s worth the work,” said Robert C. Doebele, MD, PhD, investigator at the CU Cancer Center and assistant professor at the CU School of Medicine. “It’s worth following this line of reasoning to its conclusion to see if colorectal cancer patients will also benefit from drugs proved effective in lung cancer.”
The group writes that “identification of ALK and ROS1 oncogenes may open new therapeutic options for CRC,” specifically with the class of drugs known as tyrosine-kinase inhibitors (TKIs) shown to “turn off” ALK and ROS1 gene mutations thereby killing or slowing the growth of cancer cells.
For example, the drug crizotinib was approved by the FDA in 2011 to treat ALK-positive lung cancer, and this drug or others that are in development to treat ALK+ and ROS1+ cancers may have similar benefit in CRC.
“By rethinking the way we understand cancers—as their genetic mutations and not just as the sites where they live in the body—we see that a therapy that targets a specific mutation may show benefit in treating any other cancer that shares the same mutation,” said Dara Aisner, MD, PhD, investigator at the CU Cancer Center and molecular pathologist at the CU School of Medicine.