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Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?

Interfering with mitosis for cancer treatment is an old concept that has proven highly successful in the clinics. Microtubule poisons are used to treat patients with different types of blood or solid cancer since more than 20 years, but how these drugs achieve clinical response is still unclear. Arr...

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Detalles Bibliográficos
Autores principales: Haschka, Manuel, Karbon, Gerlinde, Fava, Luca L, Villunger, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836099/
https://www.ncbi.nlm.nih.gov/pubmed/29459486
http://dx.doi.org/10.15252/embr.201745440
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author Haschka, Manuel
Karbon, Gerlinde
Fava, Luca L
Villunger, Andreas
author_facet Haschka, Manuel
Karbon, Gerlinde
Fava, Luca L
Villunger, Andreas
author_sort Haschka, Manuel
collection PubMed
description Interfering with mitosis for cancer treatment is an old concept that has proven highly successful in the clinics. Microtubule poisons are used to treat patients with different types of blood or solid cancer since more than 20 years, but how these drugs achieve clinical response is still unclear. Arresting cells in mitosis can promote their demise, at least in a petri dish. Yet, at the molecular level, this type of cell death is poorly defined and cancer cells often find ways to escape. The signaling pathways activated can lead to mitotic slippage, cell death, or senescence. Therefore, any attempt to unravel the mechanistic action of microtubule poisons will have to investigate aspects of cell cycle control, cell death initiation in mitosis and after slippage, at single‐cell resolution. Here, we discuss possible mechanisms and signaling pathways controlling cell death in mitosis or after escape from mitotic arrest, as well as secondary consequences of mitotic errors, particularly sterile inflammation, and finally address the question how clinical efficacy of anti‐mitotic drugs may come about and could be improved.
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spelling pubmed-58360992018-03-14 Perturbing mitosis for anti‐cancer therapy: is cell death the only answer? Haschka, Manuel Karbon, Gerlinde Fava, Luca L Villunger, Andreas EMBO Rep Review Interfering with mitosis for cancer treatment is an old concept that has proven highly successful in the clinics. Microtubule poisons are used to treat patients with different types of blood or solid cancer since more than 20 years, but how these drugs achieve clinical response is still unclear. Arresting cells in mitosis can promote their demise, at least in a petri dish. Yet, at the molecular level, this type of cell death is poorly defined and cancer cells often find ways to escape. The signaling pathways activated can lead to mitotic slippage, cell death, or senescence. Therefore, any attempt to unravel the mechanistic action of microtubule poisons will have to investigate aspects of cell cycle control, cell death initiation in mitosis and after slippage, at single‐cell resolution. Here, we discuss possible mechanisms and signaling pathways controlling cell death in mitosis or after escape from mitotic arrest, as well as secondary consequences of mitotic errors, particularly sterile inflammation, and finally address the question how clinical efficacy of anti‐mitotic drugs may come about and could be improved. John Wiley and Sons Inc. 2018-02-19 2018-03 /pmc/articles/PMC5836099/ /pubmed/29459486 http://dx.doi.org/10.15252/embr.201745440 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Haschka, Manuel
Karbon, Gerlinde
Fava, Luca L
Villunger, Andreas
Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title_full Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title_fullStr Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title_full_unstemmed Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title_short Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
title_sort perturbing mitosis for anti‐cancer therapy: is cell death the only answer?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836099/
https://www.ncbi.nlm.nih.gov/pubmed/29459486
http://dx.doi.org/10.15252/embr.201745440
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