Prior acquired resistance to paclitaxel relays diverse EGFR-targeted therapy persistence mechanisms.

ABSTRACT: Secondary drug resistance stems from dynamic clonal evolution during the development of a prior primary resistance. This collateral type of resistance is often a characteristic of cancer recurrence. Yet, mechanisms that drive this collateral resistance and their drug-specific trajectories are still poorly understood. Using resistance selection and small-scale pharmacological screens, we find that cancer cells with primary acquired resistance to the microtubule-stabilizing drug paclitaxel often develop tolerance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), leading to formation of more stable resistant cell populations. We show that paclitaxel-resistant cancer cells follow distinct selection paths under EGFR-TKIs by enriching the stemness program, developing a

SUBMITTER: Aldonza MBD 

PROVIDER: S-EPMC7007258 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature