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Updated: Jun 23, 2026

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

Chromosomal instability determines taxane response

Charles Swanton1, Barbara Nicke, Marion Schuett

  • 1Cancer Research UK, London Research Institute, London WC2A 3PX, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2009
PubMed

Insights

Microtubule-stabilizing agents

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Microtubule-stabilizing (MTS) agents, like taxanes, are crucial chemotherapeutics, but their precise mechanism remains unclear.
  • Genes repressed by MTS agents are overexpressed in tumors with chromosomal instability (CIN).

Purpose of the Study:

  • To investigate the role of specific genes in cancer cell survival and response to MTS agents.
  • To explore the link between chromosomal instability (CIN) and therapeutic outcomes.

Main Methods:

  • Gene expression analysis in cell lines treated with MTS agents.
  • Gene silencing experiments to assess the impact on cancer cell viability.
  • Correlation analysis of gene expression, CIN, and clinical outcomes in breast and ovarian cancer patients.

Main Results:

  • A set of 50 "CIN-survival" genes were identified, with 22 involved in DNA repair.
  • Silencing these genes led to cancer cell death, indicating their role in aneuploid cell survival.
  • Overexpression of CIN-survival genes correlates with poor prognosis in estrogen receptor-positive breast cancer and is frequent in basal-like and Her2-positive subtypes.
  • Paclitaxel repressed CIN-survival genes in diploid cells, causing cell death, but not in chromosomally unstable cells.
  • High CIN levels in ovarian cancer patients predicted resistance to taxanes but sensitivity to carboplatin.

Conclusions:

  • CIN-survival genes are critical for aneuploid cancer cell survival and are implicated in MTS agent resistance.
  • Chromosomal instability (CIN) is a key determinant of response to microtubule-stabilizing agents in vivo.
  • Pretherapeutic assessment of CIN could refine treatment strategies and clinical trial design for MTS agents.

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