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Forcing dividing cancer cells to die; low-dose drug combinations to prevent spindle pole clustering.

Authors
  • Ducrey, Eloise1, 2, 3
  • Castrogiovanni, Cédric3, 4
  • Meraldi, Patrick5, 6
  • Nowak-Sliwinska, Patrycja7, 8, 9
  • 1 School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. , (Switzerland)
  • 2 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. , (Switzerland)
  • 3 Translational Research Center in Oncohaematology, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. , (Switzerland)
  • 4 Department of Cell Physiology and Metabolism, University of Geneva Medical School, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. , (Switzerland)
  • 5 Translational Research Center in Oncohaematology, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. [email protected] , (Switzerland)
  • 6 Department of Cell Physiology and Metabolism, University of Geneva Medical School, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. [email protected] , (Switzerland)
  • 7 School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. [email protected] , (Switzerland)
  • 8 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. [email protected] , (Switzerland)
  • 9 Translational Research Center in Oncohaematology, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. [email protected] , (Switzerland)
Type
Published Article
Journal
APOPTOSIS
Publisher
Springer-Verlag
Publication Date
Jun 01, 2021
Volume
26
Issue
5-6
Pages
248–252
Identifiers
DOI: 10.1007/s10495-021-01671-3
PMID: 33870441
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mitosis, under the control of the microtubule-based mitotic spindle, is an attractive target for anti-cancer treatments, as cancer cells undergo frequent and uncontrolled cell divisions. Microtubule targeting agents that disrupt mitosis or single molecule inhibitors of mitotic kinases or microtubule motors kill cancer cells with a high efficacy. These treatments have, nevertheless, severe disadvantages: they also target frequently dividing healthy tissues, such as the haematopoietic system, and they often lose their efficacy due to primary or acquired resistance mechanisms. An alternative target that has emerged in dividing cancer cells is their ability to "cluster" the poles of the mitotic spindle into a bipolar configuration. This mechanism is necessary for the specific survival of cancer cells that tend to form multipolar spindles due to the frequent presence of abnormal centrosome numbers or other spindle defects. Here we discuss the recent development of combinatorial treatments targeting spindle pole clustering that specifically target cancer cells bearing aberrant centrosome numbers and that have the potential to avoid resistance mechanism due their combinatorial nature.

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