Microtubule disruption reduces metastasis more effectively than primary tumor growth

Breast Cancer Res. 2022 Feb 14;24(1):13. doi: 10.1186/s13058-022-01506-2.

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.

Keywords: Breast cancer; Circulating tumor cells; MDA-MB-231; Metastasis; Microtentacles; Reattachment; Vinorelbine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Microtubules
  • Neoplasm Metastasis
  • Vinorelbine / pharmacology

Substances

  • Vinorelbine