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Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism - Clinical and Translational Oncology

Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism - Clinical and Translational Oncology

Source : https://link.springer.com/article/10.1007/s12094-022-02884-x

Purpose Although lorlatinib, the third generation of echinoderm microtubule protein 4-anaplastic lymphoma kinase (EML4-ALK) tyrosine kinase inhibitor (TKI), overcame the previous generation ALK-TKIs' drug resistance problems, but the mechanism of lorlatinib resistance remained unclear. Furthermore, optimal chemotherapy for lorlatinib-resistant non-small cell lung cancer (NSCLC) patients was still unknown.


Conclusion: This study demonstrated that the combination of p53 protein agonist and lorlatinib may provide a new therapeutic strategy for NSCLC patients with lorlatinib resistance and TP53 mutation. Furthermore, the results also provide guidance for selecting optimal chemo-regimens for NSCLC patients after ALK-TKIs failure.