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ASCO 2013: Lung Cancer Mutations ALK and ROS1 Also Drive Colorectal Cancer

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Key Points

  • Researchers used fluorescence in situ hybridization to test for the oncogenic gene rearrangements in 236 tumor samples from patients with metastatic colorectal cancer.
  • One patient tested positive for ALK rearrangement, confirming earlier findings, and two patients tested positive for ROS1, the first cases of ROS1 rearrangements in colorectal cancer.
  • The findings may open new therapeutic options for colorectal cancer, specifically with the tyrosine kinase inhibitors such as crizotinib.

A study from the University of Colorado Cancer Center shows that the 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. The results were presented at the 2013 ASCO Annual Meeting (Abstract 3545).

First Case of ROS1 Rearrangements

"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, PhD, investigator at the CU Cancer Center and Professor at the CU School of Medicine.

In this study, Dr. Garcia and colleagues used fluorescence in situ hybridization (FISH) to test for the oncogenic gene rearrangements in 236 tumor samples from patients with metastatic colorectal cancer. Among the patients tested, one was positive for ALK rearrangement, confirming previous findings, and two were positive for ROS1, which demonstrates the first finding of ROS1 as an oncogenic driver of colorectal cancer.

New Therapeutic Options for Colorectal Cancer

"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 C. Doebele, MD, PhD, investigator at the CU Cancer Center and Assistant Professor at the CU School of Medicine.

According to the researchers, "identification of ALK and ROS1 activations may open new therapeutic options for colorectal cancer," specifically with the class of drugs known as tyrosine- kinase inhibitors, which have been shown to stop ALK and ROS1 gene mutations from producing their cancer-driving proteins. The drug crizotinib (Xalkori) was approved in 2011 to treat ALK-positive lung cancer, and now this agent and other similar tyrosine kinase inhibitors 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," Dr. Doebele said.

Dr. Varella-Garcia received honoraria and research funding from Abbott Molecular. Dr. Doebele received honoraria from Abbott Molecular, research funding from Pfizer, and has a consultant or advisory role with Pfizer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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