In results presented at ASCO 2013, a University of Colorado Cancer Center study shows that ALK and ROS1 gene rearrangements known to drive subsets of lung cancer are also present in some colorectal cancers. Results imply that drugs used to target ALK and ROS1 in lung cancer may also have applications in this subset of colorectal cancer patients.
“When you have known oncogenes that are already targeted by FDA-approved drugs, it just made sense to look for these oncogenes in other cancers,” said Marileila Varella Garcia, investigator at the CU Cancer Center and professor at the CU School of Medicine.
In this case, Garcia and colleagues used the technique known as fluorescence in situ hybridization (FISH) to test for the oncogenic gene rearrangements in 236 tumor samples of colorectal cancer. The work found one ALK rearrangement, confirming previous findings, and demonstrates the first finding of ROS1 as an oncogenic driver of colorectal cancer– in this case found in 2 of the 236 tumor samples.
“This is a case in which we have all the background science– we know ALK and ROS1 are oncogenes. We have drugs that target these oncogenes. And we even have a test to determine who has the gene rearrangements and so should benefit from these drugs. The only piece missing was finding these oncogenes in other cancers, and now we’ve filled in that piece,” said Robert Doebele, investigator at the CU Cancer Center and assistant professor at the CU School of Medicine.
The group writes that “identification of ALK and ROS1 activations may open new therapeutic options for CRC,” specifically with the class of drugs known as tyrosine-kinase inhibitors (TKIs) shown to stop ALK and ROS1 gene mutations from producing their protein products that drive cancer. For example, the drug crizotinib was approved in 2011 to treat ALK-positive lung cancer, and now crizotinib or other, similar TKIs in development seem likely treatments for the subset of colorectal cancer patients who share this ALK mutation.
“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. It’s worth following this line of reasoning to its conclusion to see if colorectal cancer patients will benefit from these drugs,” Doebele said.