Preclinical Prediction of Resistance Mutations and Proposal of Sequential Treatment Strategies for ALK-positive Lung Cancer Using Next-generation ALK Inhibitors.

ABSTRACT:

Background

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in approximately 5% of non-small cell lung cancers (NSCLCs). Although ALK tyrosine kinase inhibitors provide substantial clinical benefits, acquired resistance-conferring mutations frequently emerge, leading to disease progression. Preclinical prediction of these mutations might help guide the development of more effective sequential treatment strategies prior to clinical application.

Objective

To predict the emergence of resistance mutations to the investigational ALK inhibitors zotizalkib (TPX-0131), gilteritinib (ASP2215), and neladalkib (NVL-655) following resistance to first-line alectinib and assess the potential of these drugs as second-line therapies.

Methods

A polymerase chain reaction (PCR

SUBMITTER: Takei Y 

PROVIDER: S-EPMC12508005 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature