Treating colon cancer through personalized medicine

A discovery of how a certain tumor suppressor molecule works to prevent tumor growth could lead to a personalized treatment approach for colon cancer. In a study published in Nature Medicine (2015; doi:10.1038/nm.3908), researchers reported that the tumor-suppressing protein, absent in melanoma 2 (AIM2), helps prevent colon cancer by restricting a signaling molecule called Akt.

With this finding, the researchers believe they have found a possible drug target for patients with colon cancer who lack the tumor suppressor AIM2.

“Several studies and clinical evidence suggest AIM2 functions as a tumor suppressor, but until now, we've had very little direct evidence to explains how this occurs,” said first author Justin E. Wilson, PhD, a postdoctoral fellow at University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, NC, and the UNC School of Medicine Department of Microbiology and Immunology and the Department of Genetics.

“We found that AIM2 inhibits tumorigenesis in multiple animal models of colorectal cancer by restricting the prosurvival signaling molecule, Akt, which is commonly hyperactive in many human cancers.”

The study builds on previous findings that suggest AIM2 limits cancer cell growth in colon cancer cell lines, Dr. Wilson said, as well as on a clinical report of poor prognosis in colon cancer patients with low or missing AIM2 levels.

“Patients with colon cancer lacking in AIM2 have been found to have poor survival, but we have identified a possible personalized therapeutic strategy to help them,” said Jenny Ting, PhD, William R. Kenan Jr. Distinguished Professor in the UNC School of Medicine Department of Genetics and a member of the UNC Lineberger Comprehensive Cancer Center.

The researchers found in a study in colon cancer cells that AIM2 limits the activation of the signaling molecule Akt. In mouse models lacking AIM2, the researchers found that they had smaller tumors and precancerous colon polyps when blocked Akt.

Dr. Wilson said the researchers believe their findings mean that drugs used to inhibit Akt could be used as a personalized therapy for people who don't have AIM2.

“Our research paves the way for future clinical trials that screen for AIM2 expression in colon cancer and possibly other cancers to identify patients who may potentially benefit from personalized anti-Akt therapy,” Dr. Wilson said.

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