Treatment modalities for advanced ALK-rearranged non-small-cell lung cancer

Future Oncol. 2016 Apr;12(7):945-61. doi: 10.2217/fon.16.15. Epub 2016 Feb 19.

Abstract

The ALK gene plays a key role in the pathogenesis of non-small-cell lung cancer (NSCLC). Patients with NSCLC harboring an ALK-rearrangement represent the second oncogene addiction to be identified in this disease. Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease. However, despite initial impressive responses to crizotinib, acquired resistance almost invariably develops within 12 months. The pressing need for effective second-line agents has prompted the rapid development of next-generation ALK inhibitors. These agents, notably ceritinib and alectinib as the most developed, have a higher potency against ALK than crizotinib, along with activity against tumors harboring crizotinib-resistant mutations and potentially improved CNS penetration.

Keywords: ALK-rearrangement; CNS disease; alectinib; ceritinib; crizotinib; crizotinib-resistance; non-small-cell lung cancer.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / radiotherapy
  • Central Nervous System Neoplasms / secondary
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Standard of Care
  • Treatment Outcome

Substances

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