Acta Medica Okayama volume74 issue5
2020-10 発行

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

Makimoto, Go Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
Ohashi, Kadoaki Department of Respiratory Medicine, Okayama University Hospital ORCID Kaken ID researchmap
Maeda, Yoshinobu Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID researchmap
Kiura, Katsuyuki Department of Respiratory Medicine, Okayama University Hospital ORCID Kaken ID publons researchmap
Publication Date
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.
Document Type
lung cancer
anaplastic lymphoma kinase
tyrosine kinase inhibitors
resistance mechanism
Link to PubMed
74_5_371.pdf 2.13 MB