May 8, 2015
“Endothelin Axis and Pancreatic Tumor Microenvironment”
University of Nebraska Medical Center
Even with early diagnosis, pancreatic cancer (PC) remains a treatment-refractory malignancy with dismal prognosis. There is a growing consensus that the complex tumor microenvironment (TME) contributes to the aggressive phenotype of PC and is a major determinant of therapy resistance. Selective modulation of TME to improve the delivery and distribution of therapeutic agents can potentially improve the efficacy of chemotherapy. Similarly approaches targeting immunosuppressive cellular and molecular factors in the TME can improve the efficacy of immunotherapy. Endothelins (ETs) are a family of three peptides, ET-1, ET-2 and ET-3, which mediate pleotropic effects via two G-protein coupled receptors ETAR and ETBR. This presentation will describe how the components of endothelin axis are expressed in various cellular compartments of pancreatic TME. Further, the presentation describes the impact of targeting endothelin axis on pancreatic TME in genetically engineered animal models and discusses the potential impact on various therapeutic modalities including chemotherapy and immunotherapy.
Jain received his Masters in Biochemistry in 1996 from Devi Ahilya University, Indore and received his Ph.D in Biotechnology in 2002 from the Institute of Microbial Technology, Chandigarh India. Subsequently he completed his post-doctoral training at the University of Nebraska Medical Center (UNMC) in 2007 in Cancer Biology and later joined the Department of Biochemistry and Molecular Biology as a faculty member. The overall objective of his research is to improve the delivery and distribution of therapeutic agents for solid tumors, particularly pancreatic cancer. Jain’s team is studying the role of signaling pathways involved in the complex cellular crosstalk in the tumor microenvironment with a goal to selectively modulate the obstructive effects of stroma. His laboratory is also interested in evaluating biomarkers for early diagnosis, and developing targeted therapeutic approaches (radioimmunotherapy, immunotherapy) that exploit differential overexpression of mucins in pancreatic cancer.