Can PARP Inihibitors be used as neoadjuvant to chemotherapy?

PARP Inhibitors: Progressively Accurate class of Response Polymerases and their role in Neoadjuvant setting

PARP (Poly-adenosine diphosphate (ADP) ribose polymerase) are nucleoproteins that mediate the transfer of ADP ribose group to an adaptor protein, therefore, helping to generate long poly (ADP ribose) chains. Post this modification, these nucleoproteins are known to mediate several cellular functions such as regulation of chromatin modeling and folding. Inhibitors for the PARP enzymes have been under clinical investigation as a management tool for breast and ovarian cancer. This article will highlight the role of Olaparib in the neoadjuvant as well as the metastatic setting.

Fairly new to the market, PARP inhibitors belong to a broad class of targeted therapies underway clinical development. They made way into the breast cancer management market and are now under investigation for several cancer types. Three PARP inhibitors, Olaparib (Lynparza), Rucaparib (Rubraca) and Niraparib (Zejula) are approved by the FDA for the treatment of ovarian, primary peritoneal and fallopian tube cancer.

Olaparib (Lynparza) is an approved treatment for ovarian cancer in women who have previously received chemotherapy and carry BRCA1/2 mutation. The drug was tested in a major study (Olympia trial) that tested the safety and efficacy of olaparib in an adjuvant (given in addition to the mainstay treatment) setting and also exploration is tested in the neoadjuvant setting. Olaparib significantly improved progression-free survival compared to the standard single-agent treatment setting.  Clearly outlined, Olaparib being an inhibitor of PARP, does not allow the cancer cells to seek help with survival upon being damaged. This serves as an intrinsic advantage for the PARP inhibitors as a treatment for cancer.

Success around the PARP Inhibitors paved their journey as a treatment option for other cancers as well as a treatment option under different clinical settings. Currently, PARP Inhibitors are being tested in the neoadjuvant setting (treatment first given to a patient to shrink the tumor size, usually before a surgery), metastatic setting (in advanced stages of cancer) and as a combination therapy (given along with another drug) as well.  Olaparib in the Neoadjuvant setting is a new arena for exploration.

It is fortunate to filter out treatment options that can make use of an intrinsically available mechanism and fight away from havoc such as cancer.