A class of drugs that shows promise in breast and ovarian cancers with BRCA gene mutations could potentially benefit colorectal cancer patients with a different genetic mutation, a new study from the University of Michigan Comprehensive Cancer Center finds.

Working in cell lines from colorectal cancer patients, researchers found that a new class of drugs called PARP inhibitors – which inhibits PARP or poly(adenosine-disposphate-ribose) polymerase – worked against tumors with mutations in the MRE11 gene.

About 15% of all colorectal cancers have what’s called microsatellite instability, a type of error in the DNA. About 82% of those tumors have the MRE11 gene mutation.

“This is a potential broader application for PARP inhibitors, beyond breast and ovarian cancer. This is a class of drug that’s already shown safety in early clinical trials and now might benefit some colorectal cancer patients as well,” says lead study author Eduardo Vilar-Sanchez, M.D., Ph.D., a hematology/oncology fellow at the U-M Medical School.

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The study, which was published in Cancer Research, also found that PARP inhibitors are even more effective when both copies of MRE11 were mutated. Each person carries two copies of each gene, which means mutations can occur in either one or both copies. The researchers suggest that PARP inhibitors could be targeted specifically to colorectal cancer patients who have two copies of the mutated gene.

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Researchers are planning a phase I clinical trial to look at using PARP inhibitors in colorectal cancer patients with two mutated copies of MRE11. Future trials are being considered using PARP inhibitors to prevent colorectal cancer and other cancers in people with Lynch syndrome whose tumors have this mutation.

Microsatellite instability is also seen in prostate cancer and endometrial cancer, suggesting potential for PARP inhibitors to play a role in additional types of cancer as well, Vilar-Sanchez says, adding that more research is needed in these areas.

The U-M Cancer Genetics Clinic regularly screens for microsatellite instability in patients at high risk of colorectal cancer. In addition, these markers can be easily detected in tissue samples of patients already diagnosed with colorectal cancer.

Colorectal cancer statistics: 142,570 Americans will be diagnosed with colorectal cancer this year and 51,370 will die from the disease, according to the American Cancer Society.

For more information:
Vilar E, Bartnik CM, Stenzel SL, Raskin L, Ahn J, Moreno V, Mukherjee B, Iniesta MD, Morgan MA, Rennert G, Gruber SB. MRE11 Deficiency Increases Sensitivity to Poly(ADP-ribose) Polymerase Inhibition in Microsatellite Unstable Colorectal Cancers. Cancer Res. 2011 Apr 1;71(7):2632-2642. Epub 2011 Feb 7. [doi:10.1158/0008-5472.CAN-10-1120].

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