Rationale for Combining Olaparib With Neratinib in HER2+ Uterine Serous Carcinoma скачать в хорошем качестве

Rationale for Combining Olaparib With Neratinib in HER2+ Uterine Serous Carcinoma

Ghanshyam Yadav, MD, a first-year resident at Baylor College of Medicine, discusses the rationale for the preclinical work investigating the combination of PARP inhibitor olaparib (Lynparza) plus the pan-HER TKI neratinib (Nerlynx) in HER2-positive uterine serous carcinoma. The hypothesis for this combination is that there may be a connection between the HER/ErbB2 pathway inhibited by neratinib and the DNA damage repair pathway inhibited by olaparib, says Yadav. Previous studies in breast cancer showed inhibiting the PI3K can impact the BRCA, which previously were thought to be entirely different. By treating the cell with a PARP inhibitor, Yadav says HER2 expression could be increased on the cell surface, which provides a larger target for neratinib. Preclinical data showed that PAR expression is increased when the cells are treated with neratinib. This demonstrates that there was more DNA damage done, and it is known that taking away the PARP inhibitor can cause more damage. Yadav conducted a mouse study, in which he and his team of researchers found survival was statically longer with the combination, and there was a statistically significant difference in tumor growth from day 4 in 1 cell line. This is very strong synergism, Yadav concludes. For more resources and information regarding anticancer targeted therapies in gynecologic oncology:   targetedonc.com/resource-center/gyencologic