title: Mechanisms of intrinsic and acquired resistance to kinase-targeted therapies.
abstract: Cancer drugs that target pivotal signaling molecules required for malignant cell survival and growth have demonstrated striking antitumor activities in appropriately selected patient populations. Unfortunately, however, therapeutic responses are often of limited duration, typically 6-12 months, because of emergence of drug-resistant subclones of tumor cells. In this review, we highlight several of the mechanisms of emergent resistance to several kinase-targeted small molecule therapies used in melanoma, non-small cell lung cancer (NSCLC) and other solid tumors as illustrative examples. We discuss the implications of these findings for the development of new treatment strategies to delay or prevent the onset of drug resistance.
authors.affiliation: Oncology Research Unit, Pfizer Worldwide Research and Development, 10777 Science Center Drive, San Diego, CA, USA.
authors.forename: Shubha
authors.initials: S
authors.lastname: Bagrodia
authors.forename: Tod
authors.initials: T
authors.lastname: Smeal
authors.forename: Robert T
authors.initials: RT
authors.lastname: Abraham
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D009857:Oncogenes / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases