Prospects of PARP Inhibitors in Treatment of BRCA-Mutated Pancreatic Cancer: a Literature Review

Abstract

Pancreatic adenocarcinoma has a 5-year overall survival rate of 9 %, with an outlook of becoming the second leading cause of cancer mortality in the USA by 2030. Familial pancreatic cancer and genetic predisposition syndromes have attracted more interest in the perspective of targeted therapy. Various authors estimate genetic causes to account for 10–15 % of pancreatic cancers. The BRCA gene mutations comprise the today’s most relevant genetic predisposition syndrome. The frequency of BRCA1/2 and PALB2 germinal mutations in patients with pancreatic adenocarcinoma constitutes about 5–9 %. Over recent years, PARP inhibitors (PARPi) have composed a new targeted therapy class with a significant effect in breast and ovarian cancers. With the mechanism of action of the PARP inhibitor and platinum drugs targeting different DNA repair pathways, their combination therapy has been suggested as promising. We report studies of a combination treatment with veliparib, gemcitabine and cisplatin in germinal BRCA1/2-mutation patients with advanced wild-type pancreatic adenocarcinoma (WT). Recent advances have identified patients with germinal and somatic mutations in the BRCA1/2 and other genes. HRD-targeted therapy, including platinum and PARP inhibitor drugs, can significantly improve survival.

Keywords

• аденокарцинома поджелудочной железы
• brca1/2 белок
• химиотерапия
• таргетная терапия
• parp-ингибиторы
• герминальные мутации
• генетический скрининг
• соматические мутации