ArticlebioRxiv : the preprint server for biology2024
Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that enhance the efficacy of MEK inhibitors Methods: HTS was performed using 3-dimensional CRC spheroids. Trametinib, the anchor drug, was probed with 2 clinically ready libraries of 252 drugs to identify effective drug combinations. The effects of the drug combinations on CRC cell proliferation and apoptosis were further validated using cell growth assays, flow cytometry, and biochemical assays. Proteomic and immunostaining studies were performed to determine the effects of the drugs on molecular signaling and cell division. The effects of the drug combinations were examined Results: HTS identified paclitaxel as being synergistic with trametinib. Conclusion: Our data provide evidence supporting clinical trials of trametinib with paclitaxel as a novel therapeutic option for patients with
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