Changing the course of pancreatic cancer - Focus on recent translational advances

Milind Javle, Talia Golan, Anirban Maitra

Research output: Contribution to journalReview article

Abstract

In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal" there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents.Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalCancer Treatment Reviews
Volume44
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • Carcinoma
  • Pancreatic ductal
  • Translational medical research

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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