4.5 Article

Microtubule disruption reduces metastasis more effectively than primary tumor growth

Journal

BREAST CANCER RESEARCH
Volume 24, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13058-022-01506-2

Keywords

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

Categories

Funding

  1. METAvivor Foundation
  2. National Institutes of Health [R01-CA124704, R01-CA154624, R01-EB027143]
  3. United States Department of Veterans Affairs [I01-BX002746, I01-BX003690]
  4. American Cancer Society [122229-IRG97-153-10-IRG, RSG-18-028-01-CSM, K01CA166575, 5T32GM008181-30, 1F31CA232393-01]
  5. Maryland Cigarette Restitution Fund
  6. [P30-CA134274]

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Clinical cancer imaging focuses on tumor growth, not metastasis. This study found that the microtubule-depolymerizing drug Vinorelbine can effectively reduce metastatic phenotypes of tumor cells and extend the survival of metastatic tumors, even with short-term treatment. Additionally, the study demonstrates the feasibility of using a small number of tumor cells from patient biopsies for drug response detection.
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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