CRM1 inhibitor anti-tumor activity is enhanced with salicylates by S-phase arrest and impaired DNA-damage repair
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Chromosome region maintenance protein1 (CRM1) mediates protein export from the nucleus and is a new target for anti-cancer therapeutics. Broader application of KPT-330 (Selinexor), a CRM1 inhibitor approved for myeloma, has been limited by toxicity. We found that combining choline salicylate (CS) with low-doses of KPT-330 (K+CS) had potent synergistic activity across blood and solid organ cancers ex-vivo and in-vivo. Mechanistically, K+CS enhances CRM1 degradation, induces potent inhibition of CRM1 mediated nuclear export, and arrests cells in S-phase with simultaneous reduction of Rad51 causing impaired DNA damage repair. K+CS represents a potential new class of therapy for multiple cancer types.
提供机构：
Mayo Clinic
创建时间：
2022-02-20
