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bioRxiv · 10.1101/2022.05.26.493531

Prediction of Resistant Mutations against Upcoming ALK-TKIs, Repotrectinib (TPX-0005) and Ensartinib (X-396)

Doi, Y.·Tagaya, H.·Noge, A.·Semba, K.
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Abstract

ALK gene rearrangement is observed in approximately 4% of patients with non-small cell lung cancer. These individuals benefit clinically from a range of approved ALK-TKIs; however, using many ALK-TKIs in a row will always result in resistant compound mutations in the kinase domain. Therefore, next-generation ALK-TKIs which are potent to these resistant mutations are still under development. In this context, preclinical prediction of resistant mutations generated by developing ALK-TKIs will provide useful information about the effective sequential treatment of ALK-TKIs. In this study, we developed a simple error-prone PCR-based mutation prediction system, and as a model study, we predicted resistant mutations against upcoming ALK-TKI, repotrectinib, and ensartinib. According to the predictive mutation patterns, repotrectinib and ensartinib may be used as second-line therapeutic options following the first-line alectinib treatment.

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Doi, Y., Tagaya, H., Noge, A., Semba, K.. 2022-05-26. Prediction of Resistant Mutations against Upcoming ALK-TKIs, Repotrectinib (TPX-0005) and Ensartinib (X-396). https://doi.org/10.1101/2022.05.26.493531

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