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Review
. 2022 Apr 6:12:863461.
doi: 10.3389/fonc.2022.863461. eCollection 2022.

Targeting ALK Rearrangements in NSCLC: Current State of the Art

Ling Peng  1 , Liping Zhu  2 , Yilan Sun  1 , Justin Stebbing  3 , Giovanni Selvaggi  4 , Yongchang Zhang  5 , Zhentao Yu  6
Affiliations
Review

Targeting ALK Rearrangements in NSCLC: Current State of the Art

Ling Peng et al. Front Oncol. .

Abstract

Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.

Keywords: ALK; lung cancer; rearrangement; resistance; tyrosine kinase inhibitor.

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Conflict of interest statement

GS is employed by, and holds stock in, Xcovery Holdings, Inc. JS is Editor-in-Chief of Oncogene and has sat on SABs for Vaccitech, Heat Biologics, Eli Lilly, Alveo Technologies, Pear Bio, Agenus, Equilibre Biopharmaceuticals, Graviton Bioscience Corporation, Celltrion, Volvox, Certis, Greenmantle, vTv Therapeutics, APIM Therapeutics, Bryologyx and Benevolent AI. He has consulted with Lansdowne partners and Vitruvian. He chairs the Board of Directors for Xerion and previously BB Biotech Healthcare Trust PLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Timeline of approved ALK TKIs.
Figure 2
Figure 2
Treatment strategy for ALK+ NSCLC.
See this image and copyright information in PMC

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