Moving Beyond Chemotherapy for Pancreaticobiliary Tumors: Targeted and Immunotherapy Strategies

Abstract

Pancreaticobiliary cancers are a group of malignancies affecting the pancreas and biliary tract and are often associated with poor prognosis. Existing treatment strategies for these malignancies are limited. However, with the development of more advanced genomic analysis techniques, several mutations have been identified that may be targeted for the development of novel treatments. Key targets of interest include DNA damage repair (DDR) pathways for both pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) as well as isocitrate dehydrogenase 1 (IDH1) and fibroblast growth factor receptor (FGFR) in BTC and mismatch repair (MMR) genes and germline mutations in PDAC. Additionally, a better understanding of the immune microenvironment of pancreatic and biliary cancers has revealed cell types and signaling pathways that may be leveraged for treatment. This includes PD-L1 and CTLA-4 immune checkpoints, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and dendritic cells (DCs). Together, targeted agents and immunotherapy strategies have the potential to significantly improve the existing treatment landscape for pancreaticobiliary cancers.