Addressing the elephant in the room, therapeutic resistance in non-small cell lung cancer, with epigenetic therapies

摘要: // Corey A. Carter 1 , Karen Zeman 2 Regina M. Day 3 Patrick Richard Arnold Oronsky 4 Neil 5 Michelle Lybeck 6 Jan Scicinski and Bryan Walter Reed National Military Medical Center, Bethesda, MD, USA Naval Uniformed Services University of The Health Sciences, 4  InterWest Partners, Menlo Park, CA, CFLS Data, Mountain View, EpicentRx, Inc, Correspondence to: Carter, email: Keywords : non small cell lung cancer; oncology; epigenetics; resistance Received December 12, 2015 Accepted March 07, 2016 Published 19, Abstract Like Chinese boxes nesting inside each other, the classification non-small cancer (NSCLC) is subdivided into smaller subtypes on basis histological molecular attributes. latter characterizes NSCLC by its alterations identification inhibitors that target these cancer-specific “driver” mutations. Despite initial promise precision-guided therapies to inhibit a finer array subcategories, despite even curative potential immunotherapeutic checkpoint blockade, in particular, casualties still abound true clinical success stories are few far between; ever-present, if sometimes unmentioned, “elephant room”, acquisition resistance, which, sooner or later, rears ugly head undermine treatment shorten survival. Emerging data suggests epigenetic able reprogram aberrant tumor-associated epigenome ‘tame beast resistance’, thereby prolonging This article reviews role dysregulation NSCLC, explores PFS2 as possible surrogate endpoint, briefly mentions biomarkers highlights combinatorial strategies “prime” tumors reverse resistance.