title: STAT3 signaling mediates tumour resistance to EGFR targeted therapeutics.
abstract: Several EGFR inhibitors are currently undergoing clinical assessment or are approved for the clinical management of patients with varying tumour types. However, treatment often results in a lack of response in many patients. The majority of patients that initially respond eventually present with tumours that display acquired resistance to the original therapy. A large number of receptor tyrosine and intracellular kinases have been implicated in driving signaling that mediates this tumour resistance to anti-EGFR targeted therapy, and in a few cases these discoveries have led to overall changes in prospective tumour screening and clinical practice (K-RAS in mCRC and EGFR T790M in NSCLC). In this mini-review, we specifically focus on the role of the STAT3 signaling axis in providing both intrinsic and acquired resistance to inhibitors of the EGFR. We also focus on STAT3 pathway targeting in an attempt to overcome resistance to anti-EGFR therapeutics.
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Zulkifli
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Tan
authors.affiliation: Inflammation Division, Walter and Eliza Hall Institute of Medical Research, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Putoczki
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Stylli
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Electronic address: rluwor@unimelb.edu.au.
authors.forename: Rodney B
authors.initials: RB
authors.lastname: Luwor
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cancer; EGFR; STAT3; Therapeutics