AACR: Inhibition of DNA Repair in Colorectal Cancer Studied
PARP inhibitor olaparib may lead to accumulated DNA damage to cancer cells and tumor death
WEDNESDAY, Nov. 25 (HealthDay News) -- Patients with microsatellite instable colorectal cancer (CRC) may respond to treatment with the investigational drug olaparib, which can block a DNA repair pathway in the cancer cells, resulting in accumulated DNA damage and tumor death, according to a briefing presented Nov. 18 at the American Association for Cancer Research -- National Cancer Institute -- European Organisation for Research and Treatment of Cancer International Conference, "Molecular Targets and Cancer Therapeutics," held from Nov. 15 to 19 in Boston.
Mark O'Connor, Ph.D., chief scientist at KuDOS Pharmaceuticals Ltd. in Cambridge, U.K., and colleagues investigated the effect of olaparib, a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, on DNA repair in CRC cells. The PARP inhibitor had already been tested in patients with breast and ovarian cancer who have BRCA1 and BRCA2 mutations, which hinder DNA repair via one homologous recombination repair pathway. In similar fashion, PARP inhibitors block DNA repair via an alternative pathway.
The researchers found that most CRC cell lines sensitive to olaparib had microsatellite instability and mutations to the homologous recombination gene MRE11. The researchers also found that the olaparib-sensitive CRC cell lines were homologous recombination deficient.
"These results reinforce the idea that PARP inhibition might have broader clinical utility than in BRCA-deficient tumors alone," O'Connor said in a statement. "They support the idea of using targeted cancer therapies in defined molecular genetic backgrounds that exploit specific DNA repair deficiencies in the cancer to be treated."