Will pairing PARP inhibitors with immunotherapies achieve more effective outcomes in breast cancer patients? Our coverage at AACR continues. 

 

In the last several years, US and European regulators have approved several novel cancer drugs designed for women with ovarian and breast cancer who carry mutations in the tumor suppressor genes BRCA1 and BRCA2. The drugs, referred to as poly ADP-ribose polymerase or PARP inhibitors, exploit tumor DNA repair pathway deficiencies to preferentially kill cancer cells.

This is indeed good news for women who carry these mutations, but it turns out that PARP inhibitors might also be a beneficial partner for immuno-oncology drugs, mainly immune checkpoint inhibitors which unleash the power of T-cells—one of the workhorses of the immune system—by outfoxing one of the tricks tumors cells play to stay viable.

The first checkpoint inhibitors were approved about six years ago, and while they have worked well for some patients, they are far from the magic bullet to cure or tame all cancers. Immunotherapies only work on a very small percentage of patients, and we still don’t fully understand why some patients respond better to the drugs than others, or why other patients have no response at all.

Many studies are now underway to see if joining a checkpoint inhibitor with a different kind of drug might improve the chances of success. Enter the PARPs. Early stage clinical studies recently found that pairing a PARP inhibitor with an immunotherapy anti-PD1 checkpoint inhibitor increased tumor shrinkage in 25% of patients with ovarian cancer, one of the deadliest cancers for women.

At the preclinical level, a study led by Julia Schueler, PhD, a Research Director of Discovery Oncology based at Charles River’s site in Freiburg, Germany also looked at the crosstalk between a PARP inhibitor and an immune checkpoint inhibitor in two different breast cancer mouse models. Their findings suggested that the drug combination might be effective in women with BRCA-1 mutations. The results varied depending upon which kind of immune checkpoint inhibitor given to mice—PD-1 vs. CTLA-4.  

Watch the video above to learn more about this PARP study in mice and attend Julia’s oral presentation at AACR on Monday, April 1 from 3:35-3:50 at Room A411 – Georgia World CC in Atlanta. And check out Julia’s blog post from last year’s AACR on the same topic.