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Regulation of KRas‐Mediated Signaling by G‐Protein Coupled Receptors in Pancreatic Cancer
Author(s) -
Feigin Michael E.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.695.10
Subject(s) - g protein coupled receptor , kras , biology , pancreatic cancer , bioinformatics , computational biology , cancer research , drug discovery , signal transduction , cancer , microbiology and biotechnology , genetics , colorectal cancer
Pancreatic ductal adenocarcinoma is a highly lethal malignancy with few effective treatment options. We used computational approaches to identify new drug targets within this heterogeneous patient population, focusing on the G‐protein coupled receptors (GPCRs). GPCRs transduce extracellular signals from a variety of ligands through the plasma membrane, resulting in the modulation of intracellular signaling pathways and regulation of many physiological processes. This wide array of functions has resulted in the extensive utilization of GPCR targeted therapeutics, accounting for 30–50% of all currently used drugs. However, drugs targeting GPCRs are rarely utilized in cancer treatment, despite evidence that GPCRs mediate many aspects of tumorigenesis. Genomic analyses have uncovered GPCR mutations, copy number alterations and gene expression and methylation changes in a wide variety of cancers. Determining the biological implication of these genomic alterations will allow utilization of GPCR targeted therapeutics in those patients with GPCR‐driven tumors. Our preliminary evidence has uncovered the orphan GPCR GPRC5A as a critical regulator of the progression from early stage PanIN lesions to PDA. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .