Edward J Kim1, Diane M Simeone. 1. Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
Abstract
PURPOSE OF REVIEW: This review intends to describe recent studies on the interaction between pancreatic cancer cells and tumor stroma, and potential opportunities and limitations to therapeutically targeting the stroma. RECENT FINDINGS: Pancreatic cancer is characterized by densely desmoplastic stroma. It is becoming increasingly clear that there are complex and mutually supportive interactions between cancer cells and the stroma. Specific signaling pathways exist between cancer cells and cancer-associated fibroblasts that contribute to hypoxic desmoplasia. Recent developments in therapeutic approaches to targeting the stroma have demonstrated potential for enhancing efficacy of cytotoxic therapies. However, the heterogeneity and genomic complexity between tumors has also become more evident based on recent findings. There is increasing evidence for hierarchy of cancer cells with identification of a subpopulation of cancer stem cells that are inherently resistant to traditional therapies. SUMMARY: Targeting pancreatic cancer stroma is a novel therapeutic strategy that appears justified based on recent studies; however, continued focus is needed to develop more effective therapies against cells resistant to standard chemotherapy.
PURPOSE OF REVIEW: This review intends to describe recent studies on the interaction between pancreatic cancer cells and tumor stroma, and potential opportunities and limitations to therapeutically targeting the stroma. RECENT FINDINGS:Pancreatic cancer is characterized by densely desmoplastic stroma. It is becoming increasingly clear that there are complex and mutually supportive interactions between cancer cells and the stroma. Specific signaling pathways exist between cancer cells and cancer-associated fibroblasts that contribute to hypoxic desmoplasia. Recent developments in therapeutic approaches to targeting the stroma have demonstrated potential for enhancing efficacy of cytotoxic therapies. However, the heterogeneity and genomic complexity between tumors has also become more evident based on recent findings. There is increasing evidence for hierarchy of cancer cells with identification of a subpopulation of cancer stem cells that are inherently resistant to traditional therapies. SUMMARY: Targeting pancreatic cancer stroma is a novel therapeutic strategy that appears justified based on recent studies; however, continued focus is needed to develop more effective therapies against cells resistant to standard chemotherapy.
Authors: Dominic E Sanford; Brian A Belt; Roheena Z Panni; Allese Mayer; Anjali D Deshpande; Danielle Carpenter; Jonathan B Mitchem; Stacey M Plambeck-Suess; Lori A Worley; Brian D Goetz; Andrea Wang-Gillam; Timothy J Eberlein; David G Denardo; Simon Peter Goedegebuure; David C Linehan Journal: Clin Cancer Res Date: 2013-05-07 Impact factor: 12.531
Authors: W Leconet; C Larbouret; T Chardès; G Thomas; M Neiveyans; M Busson; M Jarlier; N Radosevic-Robin; M Pugnière; F Bernex; F Penault-Llorca; J-M Pasquet; A Pèlegrin; B Robert Journal: Oncogene Date: 2013-11-18 Impact factor: 9.867