PARP inhibitors may be a novel treatment strategy for women with HER2-positive breast cancers, researchers have found.
Poly (ADP-ribose) polymerase, or PARP, inhibitors target BRCA-associated familial breast and ovarian cancers, which are deficient in DNA repair. These drugs are generally well tolerated and have relatively few side effects, but only about 5% to 10% of all breast and ovarian cancers are BRCA-associated familial breast and ovarian cancers.
To explore whether the clinical application of PARP inhibitors could be broadened, researchers tested the use of these agents in human epidermal growth factor receptor 2 (HER2)-positive breast tumors. This investigative team had previously found that inhibiting the epidermal growth factor receptor (EGFR) pathway resulted in a DNA repair defect similar to that seen in familial cancers, and that this defect increased tumor sensitivity to PARP inhibitors. Because EGFR and HER2 are related proteins, the scientists theorized that HER2-targeted therapies might force a similar DNA repair defect in HER2-positive tumors, increasing the sensitivity of these tumors to PARP inhibitors.
The study revealed that HER2-positive breast cancer cell lines were, in fact, sensitive to PARP inhibitors, both in culture and when transplanted into mice. “However, the surprise was that these HER2-positive tumors were sensitive to PARP inhibitors alone, independent of a DNA repair defect,” commented study coauthor Eddy S. Yang, MD, PhD, a radiation oncologist at the University of Alabama-Birmingham, in a statement issued by the American Association for Cancer Research (AACR). “This means that there may be other mechanisms, outside of DNA repair, that dictate the sensitivity of a tumor to PARP inhibitors.”
Yang’s team’s findings were published in the AACR journal Cancer Research (2012;72:4796-4806).