The 2011 Gordon Wilson Lecture: overcoming resistance to targeted cancer drugs. Article uri icon


MeSH Major

  • Antineoplastic Agents
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Molecular Targeted Therapy


  • 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.

publication date

  • December 2012



  • Article



  • eng

PubMed Central ID

  • PMC3540597

PubMed ID

  • 23303979

Additional Document Info

start page

  • 114

end page

  • 23; discussion 123-5


  • 123