Drug Class Unexpectedly Effective on Breast Cancers
(HealthDay News) – Drugs that normally target cancer cells defective in DNA homologous recombination repair, poly(ADP-Ribose) polymerase (PARP) inhibitors, are also effective on breast cancer cells positive for human epidermal growth factor receptor 2 (HER2), even in the absence of the repair defect, according to a study published in the Sept 15 issue of Cancer Research.
Noting that PARP inhibitors are known to be effective on cells defective in homologous recombination repair (e.g., showing promise in clinical trials in BRCA-associated breast and ovarian cancers), Somaira Nowsheen, from the University of Alabama at Birmingham School of Medicine, and colleagues examined the effectiveness of PARP inhibitors on breast cancer cells negative or positive for HER2.
The researchers found that HER2-positive breast cancers were sensitive to PARP inhibitors, even those without a defect in homologous repair. HER2-negative breast cancers could be rendered sensitive to PARP inhibitors in vivo and in vitro by overexpressing HER2, with HER2 reduction abrogating this response. Further experiments showed that the ability of HER2 to inhibit the nuclear factor kappa B signaling pathway was associated with sensitivity to PARP inhibitors.
"Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2-positive breast cancer patients," Nowsheen and colleagues conclude.