Microtubule disruption reduces metastasis more effectively than primary tumor growth

微管破坏比减少原发性肿瘤生长更有效

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作者:Keyata N Thompson, Julia A Ju, Eleanor C Ory, Stephen J P Pratt, Rachel M Lee, Trevor J Mathias, Katarina T Chang, Cornell J Lee, Olga G Goloubeva, Patrick C Bailey, Kristi R Chakrabarti, Christopher M Jewell, Michele I Vitolo, Stuart S Martin

Abstract

Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.

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