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Anaplastic Lymphoma Kinase (ALK) Signaling in Lung Cancer

Sai-Hong Ignatius Ou1, Keisuke Shirai2

  • 1Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, 101 City Drive, Bldg 56, RT81, Rm 241, Orange, CA, 92868, USA. Ignatius.ou@uci.edu.

Advances in Experimental Medicine and Biology
|December 16, 2015
PubMed

Insights

Anaplastic lymphoma kinase (ALK) gene rearrangements drive non-small cell lung cancer (NSCLC). Crizotinib, an ALK inhibitor, offers clinical benefits for advanced ALK-rearranged NSCLC, guiding future cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Anaplastic lymphoma kinase (ALK) gene rearrangement is a key oncogenic driver in non-small cell lung cancer (NSCLC).
  • Crizotinib, a multi-targeted ALK/ROS1/MET inhibitor, demonstrated significant clinical efficacy in advanced ALK-rearranged NSCLC.
  • FDA approval of crizotinib in 2011 marked a milestone in targeted therapy for NSCLC.

Purpose of the Study:

  • To summarize the critical role of the ALK signaling pathway in lung cancer.
  • To provide insights into the management of epithelial malignancies driven by receptor tyrosine kinase rearrangements.
  • To highlight the evolving understanding of ALK-driven NSCLC.

Main Methods:

  • Review of clinical data and research on ALK-rearranged NSCLC.
  • Analysis of treatment outcomes, resistance mechanisms, and emerging therapies.
  • Synthesis of knowledge on ALK signaling pathway in lung cancer.

Main Results:

  • ALK rearrangements are confirmed oncogenic drivers in NSCLC.
  • Targeted inhibition with crizotinib yields significant clinical benefits.
  • Ongoing research expands knowledge of ALK pathway and resistance mechanisms.

Conclusions:

  • The ALK signaling pathway is crucial in lung cancer pathogenesis.
  • Understanding this pathway is vital for developing effective targeted therapies.
  • This knowledge may guide management strategies for other receptor tyrosine kinase-driven malignancies.
Keywords:
ALK breakapart FISHAnaplastic lymphoma kinase rearrangement non-small cell lung cancerChromosomal rearrangementCrizotinibReceptor tyrosine kinase fusion positive tumors

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