Will all women with ovarian cancer eventually benefit from poly (ADP-ribose) polymerase (PARP) inhibitors? It's a great question, and one which offers new hope for many ovarian cancer survivors.
Who do PARP inhibitors help?
There are some patients who are obvious candidates to benefit from a PARP inhibitor already: namely, those women who have deleterious underlying BRCA mutations and whose cancers exhibit platinum sensitivity. We know that patients facing those medical conditions are prime candidates because we've completed clinical tests that have shown favorable results from that treatment. Once such study was the groundbreaking SOLO-1 with olaparib, which demonstrated that if the cancer is responding to platinum, a PARP inhibitor is going to increase the chance for progression-free survival. In the SOLO-1 test, 60% of the patients who had received olaparib remained progression-free three years into the trial, compared to just 27% of the placebo arm of that study.
What happens when a PARP inhibitor stops working?
Read MoreWhat are some PARP Inhibitor combinations?
Lynparza is FDA approved in combination with Avastin (bevacizumab) for women with HRD. Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.There are a lot of other PARP inhibitor combinations currently being researched, including combining PARP inhibitors with different immunotherapies.
In one area of immunotherapy and PARP inhibitor combination therapy research, physicians have been looking at the efficacy of PARP inhibitors in combination with immune checkpoint inhibitors.
When high-grade serous ovarian carcinoma (HGSOC) tumors deficient in BRCA1 are treated with a PARP inhibitor, the tumor cells will increase their output of PD-L1 an "immune checkpoint" protein that makes the tumor cells invisible to the immune system. Drugs known as "checkpoint inhibitors" are capable of removing immune checkpoint proteins like PD-L1which are essentially blinders on the immune systemso that attacks on the tumor cells can resume.
There's promising preclinical evidence to suggest that the PARP inhibitors and the immune checkpoint inhibitors are synergistic, meaning thatwhen taken togetherthey can deliver results greater than the sum of their parts. Trials are currently underway on the efficacy of combining the PARP inhibitor niraparib (Zejula) with the immune checkpoint inhibitor pembrolizumab (Keytruda) in patients with advanced or metastatic triple-negative breast cancer or recurrent ovarian cancer.
We have also tested PARP inhibitors in combination with Phosphoinositide 3-kinase (PI3Ks) inhibitors.
The PI3KS inhibitors inhibit enzymes that are a part of the PI3K/AKT/mTOR pathwaya signaling pathway for a myriad of critical cellular functions including cell growth, proliferation, and survival. The targeted therapy of PI3KS inhibitors helps with tumor suppression, and the combination of PI3K inhibitors with PARP inhibitors opens a whole other area of clinical trial studies.
Learn more about the side effects of PARP inhibitors here.
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