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Review
. 2024 May 23:7:20.
doi: 10.20517/cdr.2024.25. eCollection 2024.

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

Darin Poei  1 , Sana Ali  2 , Shirley Ye  1 , Robert Hsu  2
Affiliations
Review

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

Darin Poei et al. Cancer Drug Resist. .

Abstract

Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified as potent oncogenic drivers in several malignancies, including non-small cell lung cancer (NSCLC). The discovery of ALK inhibition using a tyrosine kinase inhibitor (TKI) has dramatically improved the outcomes of patients with ALK-mutated NSCLC. However, the emergence of intrinsic and acquired resistance inevitably occurs with ALK TKI use. This review describes the molecular mechanisms of ALK TKI resistance and discusses management strategies to overcome therapeutic resistance.

Keywords: ALK TKI; NSCLC; acquired resistance; alectinib; brigatinib; ceritinib; crizotinib; lorlatinib.

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Conflict of interest statement

Hsu R is a consultant for Targeted Oncology and Takeda and received honoraria from DAVA Oncology and The Dedham Group. All other authors declared that there are no conflicts of interest.

Figures

Figure 1
Figure 1
ALK TKI Chemical Structure[37]. Created by BioRender.com. Authors were granted a license to use BioRender content with copyright permission. ALK: Anaplastic lymphoma kinase; TKI: tyrosine kinase inhibitor.
See this image and copyright information in PMC

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