title: Changing the course of pancreatic cancer--Focus on recent translational advances.
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.
authors.affiliation: MD Anderson Cancer Center, 1515, Holcombe Blvd, Unit 426, Houston, TX 77030, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.affiliation: Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Golan
authors.affiliation: MD Anderson Cancer Center, 1515, Holcombe Blvd, Unit 426, Houston, TX 77030, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D004260:DNA Repair / Q000235:genetics; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D057170:Translational Research, Biomedical; D059016:Tumor Microenvironment
chemical_list: D019496:Cancer Vaccines; C117307:KRAS protein, human; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Carcinoma; Pancreatic ductal; Translational medical research