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Evolution of drug resistance enabled by replicative RNAs carrying MEK1

ABSTRACT: Drug resistance poses a significant clinical challenge, and comprehending the mechanisms underlying this resistance can facilitate the design of novel inhibitors and advance cancer treatment. The REPLACE system was employed to examine resistance mutations in MEK1 during the administration of 3 allosteric inhibitors (i.e., cobimetinib, trametinib, and selumetinib). These experiments represent a category of experiments that utilize REPLACE to achieve continuous evolution (or adaptation) by linking the activity of evolutionary targets with the survival of mammalian cells.

ORGANISM(S): Mesocricetus auratus

PROVIDER: GSE271878 | GEO | 2024/09/30

REPOSITORIES: GEO

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Tracing the lineage of replicative RNAs carrying MEK1 in the evolution of drug resistance

Project description:Drug resistance poses a significant clinical challenge, and comprehending the mechanisms underlying this resistance can facilitate the design of novel inhibitors and advance cancer treatment. The REPLACE system was employed to examine resistance mutations in MEK1 during the administration of 3 allosteric inhibitors. To explore the accumulation of mutations in various RNAs during the MEK1 evolution experiment, we established a barcoded library and conducted lineage tracing of replicative RNAs carrying MEK1 throughout the drug resistance evolution process.

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Analyzing the process of mutation accumulation in MEK1 evolution experiment using amplicon sequencing

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Withdrawal of MEK1/2 inhibitor reverses acquired resistance driven by BRAF amplification but drives EMT and chemoresistance in cells with amplified KRAS

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2016-08-25 | E-GEOD-83588 | biostudies-arrayexpress

Constitutively activating MEK1 mutations drive treatment refractory histiocytic neoplasms but confer response to ERK inhibition

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2024-09-03 | GSE268618 | GEO

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