Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance.

ABSTRACT:

Background

Alectinib has shown a greater efficacy to ALK-rearranged non-small-cell lung cancers in first-line setting; however, most patients relapse due to acquired resistance, such as secondary mutations in ALK including I1171N and G1202R. Although ceritinib or lorlatinib was shown to be effective to these resistant mutants, further resistance often emerges due to ALK-compound mutations in relapse patients following the use of ceritinib or lorlatinib. However, the drug for overcoming resistance has not been established yet.

Methods

We established lorlatinib-resistant cells harboring ALK-I1171N or -G1202R compound mutations by performing ENU mutagenesis screening or using an in vivo mouse model. We performed drug screening to overcome the lorlatinib-resistant ALK-compound m

SUBMITTER: Okada K 

PROVIDER: S-EPMC6441848 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature