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Precision Oncology-Based Therapeutic Targeting in Mesothelioma
Given that mesothelioma nearly universally exhibits cell cycle abnormalities and the cell cycle interacts with multiple pathways important to the growth of mesothelioma, disruption of the cell cycle presents as a likely effective approach (or will contribute to a multiple pathway-targeted combination approach) to treating mesothelioma clinically. Our hypothesis is that combined inhibition of 1) multiple cell cycle proteins, and 2) one of 3 separate and alternative molecular pathways will serve as an effective therapy against multiple molecular subtypes of mesothelioma. Scope: We are utilizing in vitro and in vivo studies to evaluate how to best target molecular subtypes of mesothelioma. Major Findings: We have determined in multiple cell lines that cell cycle inhibitors(dinaciclib, abemaciclib, palbociclib) and inhibitors of antioxidant defense (gentian violet and auranofin) have significant activity against mesothelioma in vitro.
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