1. Microtubule disruption reduces metastasis more effectively than primary tumor growth
- Author
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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, and Stuart S. Martin
- Subjects
Mice ,Cell Line, Tumor ,Animals ,Humans ,Breast Neoplasms ,Female ,Vinorelbine ,Neoplasm Metastasis ,Microtubules - 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.
- Published
- 2022
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