Treating ALK-positive lung cancer--early successes and future challenges

Nat Rev Clin Oncol. 2012 Apr 3;9(5):268-77. doi: 10.1038/nrclinonc.2012.43.


Rearrangements of the anaplastic lymphoma kinase (ALK) gene occur infrequently in non-small-cell lung cancer (NSCLC), but provide an important paradigm for oncogene-directed therapy in this disease. Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer. Many new ALK inhibitors are being developed and understanding the challenges of determining and addressing the adverse effects that are likely to be ALK specific, while maximizing the time of benefit on targeted agents, and understanding the mechanisms that underlie drug resistance will be critical in the future for informing the optimal therapy of ALK+ NSCLC.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Disease Management
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*


  • Antineoplastic Agents
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases