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PARP Inhibitors May Help Fight Colon Cancer

John Eichorn
Published: Thursday, Apr 28, 2011

Cells with mutations in the MRE11 gene
Cells with mutations in the MRE11 gene
A class of drugs that has shown encouraging results in breast and ovarian cancers with BRCA gene mutations may also benefit patients who have colorectal cancers with a different gene mutation. A group of researchers from the University of Michigan’s Comprehensive Cancer Center found that the class of drugs known as PARP inhibitors is effective in battling colorectal tumors that have mutations in the MRE11 gene.

Each person has 2 copies of the MRE11 gene, and the study determined that PARP inhibitors worked best when both copies are mutated. The study, published in Cancer Research, was led by Eduardo Vilar-Sanchez, MD, PhD, a hematology/oncology fellow at the University of Michigan School of Medicine. He noted that PARP inhibitors have demonstrated safety in early clinical trials and that, although not currently enrolling patients, a phase I trial has been proposed to determine the efficacy of these drugs in patients with colorectal cancers.

Vilar-Sanchez told “At the moment, we are starting to develop a proposal for a phase I clinical trial to test PARP inhibitors in combination with other agents that may enhance the effect of the PARP inhibitor. In our design, we would plan to include an expansion cohort of patients with [tumors with microsatellite instability] harboring biallelic mutations of MRE11 (ie, 2 copies mutated of the gene).”

Because microsatellite instability is also seen in prostate and endometrial cancers, the study investigators believe that PARP inhibitors may also play a role in other types of cancers. However, the researchers acknowledge that more study is necessary in those areas.

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