Colorectal tumors with mutations in the MRE11 gene may be vulnerable to Poly(ADP-ribose) polymerase (PARP) inhibitors, a class of drugs that has already demonstrated safety in early clinical trials of breast and ovarian cancers.
Poly(ADP-ribose) polymerase is a protein involved in repairing damaged DNA—including cancer-cell DNA that is intentionally damaged by chemotherapy or radiotherapy with the goal of stopping these cells from surviving. PARP inhibitors show promise in the treatment of breast and ovarian cancers associated with BRCA gene mutations, and now researchers from the University of Michigan Comprehensive Cancer Center in Ann Arbor have learned that the agents also can work against tumors with MRE11 mutations. Furthermore, the agents are even more effective when both copies of these genes were mutated.
According to a statement issued by the University of Michigan Health System, approximately 15% of all colorectal cancers carry a DNA error called microsatellite instability, and the majority of those damaged tumors have the MRE11 gene mutation. “This is a potential broader application for PARP inhibitors, beyond breast and ovarian cancer,” noted lead study author Eduardo Vilar, MD, PhD, a hematology/oncology fellow at the University of Michigan Medical School.
The current research results are described in detail in Cancer Research (2011;71;2632-2642). A phase I clinical trial of PARP inhibitor use in persons with colorectal cancer and two mutated copies of MRE11 is being planned.
Microsatellite instability is also seen in prostate cancer and endometrial cancers; future research may show that PARP inhibitors can play a role in the treatment of these diseases as well.