Anaplastic Lymphoma Kinase Fusion: A Review of Therapeutic Drugs and Treatment Strategies

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Abstract

The prognosis of advanced non-small cell lung cancer (NSCLC) patients has improved in recent decades, especially for patients with an oncogenic driver mutation. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are effective for patients with the echinoderm microtubule-associated protein-like 4-ALK fusion gene. Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib. Some ALK-TKIs are effective for tumors that are resistant to other ALK-TKIs; however, as is known in epidermal growth factor receptormutant lung cancer, tumor resistance is inevitable. ALK-positive NSCLCs acquire resistance via various mechanisms, making it a heterogeneous disease. Therefore, it is necessary to develop next-generation treatment strategies, such as the use of next-generation ALK-TKIs for secondary mutations, or combination therapies with ALK-TKIs and other TKIs. In this review, we summarize the development and use of ALK-TKIs, prior pivotal clinical trials, and resistance mechanisms.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalActa medica Okayama
Volume74
Issue number5
Publication statusPublished - 2020

Keywords

  • anaplastic lymphoma kinase
  • lung cancer
  • resistance mechanism
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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