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An update of ALK inhibitors in human clinical trials

Eason Leong Yin Chan1, Claudia Ho Yi Chin1, Vivian Wai Yan Lui1,2

  • 1Pharmacogenomics & Precision Therapeutics Laboratory, Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.

Future Oncology (London, England)
|December 1, 2015
PubMed

Insights

Anaplastic Lymphoma Kinase (ALK) inhibitors like crizotinib show promise in treating metastatic non-small-cell lung cancer and other ALK-rearranged cancers, with ongoing trials exploring their full potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anaplastic Lymphoma Kinase (ALK) is a proto-oncogenic receptor tyrosine kinase implicated in various cancers.
  • Approved ALK inhibitors (crizotinib, ceritinib) have improved progression-free survival in metastatic non-small-cell lung cancer.
  • ALK aberrations are also found in other cancer types, suggesting broader therapeutic potential.

Purpose of the Study:

  • To review current understanding of ALK signaling pathways in cancer.
  • To summarize genomic aberrations involving ALK in tumorigenesis.
  • To provide a comprehensive overview of ALK inhibitors and their clinical development status.

Main Methods:

  • Literature review of ALK signaling, genomic alterations, and drug resistance mechanisms.
  • Analysis of clinical trial data for ALK inhibitors.
  • Synthesis of information on approved and investigational ALK-targeted therapies.

Main Results:

  • Crizotinib and ceritinib are approved for ALK-positive metastatic non-small-cell lung cancer.
  • Case reports suggest efficacy in other ALK-rearranged malignancies.
  • Numerous trials are evaluating ALK inhibitors as single agents and in combination therapies.

Conclusions:

  • ALK remains a critical therapeutic target in oncology.
  • Emerging resistance mechanisms require further investigation.
  • Ongoing clinical trials are crucial for defining the future role of ALK inhibitors in cancer treatment.
Keywords:
ALK alterationsALK inhibitorresistance to ALK inhibitor

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