title: Overcoming Resistance to Targeted Therapies in Cancer.
abstract: The recent discovery of oncogenic drivers and subsequent development of novel targeted strategies has significantly added to the therapeutic armamentarium of anti-cancer therapies. Targeting BCR-ABL in chronic myeloid leukemia (CML) or HER2 in breast cancer has led to practice-changing clinical benefits, while promising therapeutic responses have been achieved by precision medicine approaches in EGFR mutant lung cancer, colorectal cancer and BRAF mutant melanoma. However, although initial therapeutic responses to targeted therapies can be substantial, many patients will develop disease progression within 6-12 months. An increasing application of powerful omics-based approaches and improving preclinical models have enabled the rapid identification of secondary resistance mechanisms. Herein, we discuss how this knowledge has translated into rational, novel treatment strategies for relapsed patients in genomically selected cancer populations.
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Keara L
authors.initials: KL
authors.lastname: Redmond
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papafili
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Lawler
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom. Electronic address: s.vanschaeybroeck@qub.ac.uk.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Schaeybroeck
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D016044:Fusion Proteins, bcr-abl; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human