Challenges in developing targeted therapy for pancreatic adenocarcinoma.
BACKGROUND
Pancreatic adenocarcinoma is a leading cause of cancer deaths in the US. Gemcitabine-based chemotherapy remains the cornerstone treatment for advanced pancreatic cancers. Research into the molecular pathogenesis of pancreatic cancers has allowed scientists to understand the complex heterogeneous signals associated with them. Targeting these pathways with chemical inhibitors could improve patient outcome.


OBJECTIVE
To describe the molecular heterogeneity typical of pancreatic cancers and to discuss targeted therapies in development, and the challenges facing these agents.


METHODS
We reviewed Pub Med. literature, clinical trial database (clinicaltrials.gov), American Society of Clinical Oncology (ASCO) and American Association of Cancer Research (AACR) websites.


CONCLUSIONS
Molecular pathogenesis of pancreatic cancer involves multiple pathways and defined mutations. This molecular heterogeneity is a major reason for failure of targeted therapy. Targeting multiple oncogenic pathways using novel targeted therapies could improve patient survival.
Mahalingam
Devalingam
D
Institute of Drug Development, Division of Hematology and Medical Oncology, University of Texas Health Science Centre, San Antonio, Texas 78229, USA.
Giles
Francis
F
D000230:Adenocarcinoma / Q000628:therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D010190:Pancreatic Neoplasms / Q000628:therapy*
D000970:Antineoplastic Agents