title: The 2011 Gordon Wilson Lecture: overcoming resistance to targeted cancer drugs.
abstract: During the past decade, molecularly targeted drugs have had a transformative impact on the treatment of several cancer types. Although the clinical benefits of these drugs are impressive, their effects are generally short-lived due to the acquisition of resistance. Unlike most cytotoxic agents, for which resistance mechanisms have remained obscure despite decades of clinical use, an understanding of the molecular basis of resistance to most targeted agents has emerged quickly. This rapid progress has been possible due to advances in molecular technologies that allow genome-wide profiling of patient samples. One important and consistent theme is that resistance is almost invariably associated with restoration of the signaling pathway inhibited by the targeted agent. Here I review examples from three diseases--chronic myeloid leukemia, prostate cancer, and lung cancer--that illustrate these points and reveal how insights into resistance mechanisms can rapidly accelerate the development of second-generation targeted therapies or combination regimens to improve patient outcome.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, Howard Hughes Medical Institute, 1275 York Avenue, New York, NY 10065, USA. sawyers@mskcc.org
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001363:Awards and Prizes; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008297:Male; D058990:Molecular Targeted Therapy / Q000639:trends*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents