Explaining Synergy in the Olaparib/Neratinib Combination for Uterine Serous Carcinomas

July 2, 2019
Ghanshyam Yadav, MD

Ghanshyam Yadav, MD, a first-year resident in Obstetrics Gynecology & Reproductive Services, Baylor College of Medicine, talks through the results of a preclinical trial that found synergy in the combination of the PARP inhibitor olaparib and the pan-HER tyrosine kinase inhibitor neratinib for uterine serous cancers that overexpress HER2.

Ghanshyam Yadav, MD, a first-year resident in Obstetrics Gynecology & Reproductive Services, Baylor College of Medicine, talks through the results of a preclinical trial that found synergy in the combination of the PARP inhibitor olaparib (Lynparza) and the pan-HER tyrosine kinase inhibitor neratinib (Nerlynx) for uterine serous cancers that overexpress HER2.

Based on research from a prior breast cancer study, which revealed a connection between BRCA inhibitors and Phosphoinositide 3-kinase inhibitors, the researchers believed that HER2 and PARP had a similar relationship. This belief was their rationale for studying this combination in xenograft models, and they found that PARP inhibitors increase HER2 expression, while HER2 inhibitors increase PAR expression. Therefore, in order to decrease cell damage, the 2 pathways depend on each other.

Thetrialconcluded that the bilateral synergism between the 2 pathways can lead to improvements in overall survival and tumor growth among uterine serous cancers.