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.
