Abstract
Breast cancer is the most common malignancy in women worldwide and the second leading cause of cancer deaths after lung cancer. As in other malignancies, aneuploidy is a common feature of breast cancer and influences its behavior. Aneuploidy has been linked to inappropriate activity of the spindle assembly checkpoint (SAC), a surveillance mechanism that, in normal cells, prevents anaphase onset until correct alignment of all chromosomes at the metaphase is achieved. Interestingly, the widely used anti-microtubule drugs, vinca alkaloids and taxanes, kill cancer cells through chronic arrest in mitosis as a consequence of chronic SAC activation. Deregulated SAC has been reported in breast cancer in many reports and presents an attractive therapeutic strategy. We present here a review of the current knowledge on the SAC defects and the underlying molecular mechanisms in breast cancer, and discuss the potential of SAC components as targets for breast cancer therapies.
Keywords: Aneuploidy, anti-mitotics, breast cancer, gene expression, spindle assembly checkpoint, targeted therapy.
Current Cancer Drug Targets
Title:Targeting the Spindle Assembly Checkpoint for Breast Cancer Treatment
Volume: 15 Issue: 4
Author(s): Sandra Marques, Joana Fonseca, Patricia M.A. Silva and Hassan Bousbaa
Affiliation:
Keywords: Aneuploidy, anti-mitotics, breast cancer, gene expression, spindle assembly checkpoint, targeted therapy.
Abstract: Breast cancer is the most common malignancy in women worldwide and the second leading cause of cancer deaths after lung cancer. As in other malignancies, aneuploidy is a common feature of breast cancer and influences its behavior. Aneuploidy has been linked to inappropriate activity of the spindle assembly checkpoint (SAC), a surveillance mechanism that, in normal cells, prevents anaphase onset until correct alignment of all chromosomes at the metaphase is achieved. Interestingly, the widely used anti-microtubule drugs, vinca alkaloids and taxanes, kill cancer cells through chronic arrest in mitosis as a consequence of chronic SAC activation. Deregulated SAC has been reported in breast cancer in many reports and presents an attractive therapeutic strategy. We present here a review of the current knowledge on the SAC defects and the underlying molecular mechanisms in breast cancer, and discuss the potential of SAC components as targets for breast cancer therapies.
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Cite this article as:
Marques Sandra, Fonseca Joana, Silva M.A. Patricia and Bousbaa Hassan, Targeting the Spindle Assembly Checkpoint for Breast Cancer Treatment, Current Cancer Drug Targets 2015; 15 (4) . https://dx.doi.org/10.2174/1568009615666150302130010
DOI https://dx.doi.org/10.2174/1568009615666150302130010 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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