Published online Apr 15, 2016. doi: 10.4251/wjgo.v8.i4.366
Peer-review started: September 8, 2015
First decision: November 6, 2015
Revised: November 15, 2015
Accepted: January 27, 2016
Article in press: January 29, 2016
Published online: April 15, 2016
The emergence of the “precision-medicine” paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.
Core tip: The treatment of pancreas ductal adenocarcinoma is in an exciting phase due to a tremendous surge in knowledge regarding the molecular mechanisms that underlie pancreas cancer that has fueled interest in devising novel strategies to target signal transduction factors downstream to kirsten rat sarcoma oncogene, desmoplastic tumor stroma and cancer stem cells. Furthermore, immunotherapy by utilizing vaccines and immune checkpoint inhibitors is gaining momentum. Alluring results from studies evaluating molecularly targeted therapies have not only proven the feasibility of this approach but are also indicative of a paradigm shift in management of pancreatic cancer in the near future.