Targeting the spindle assembly checkpoint for breast cancer treatment.
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.
Sandra
S
Marques
Joana
J
Fonseca
Patrícia M A
PM
Silva
Instituto de Investigacao e Formacao Avançada em Ciencias e Tecnologias da Saude, CESPU, Rua Central da Gandra 1317, 4585-116 Gandra, Paredes, Portugal. hassan.bousbaa@iscsn.cespu.pt.
Hassan
H
Bousbaa
D000782:Aneuploidy; D050256:Antimitotic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D008938:Mitosis / Q000187:drug effects*; D058990:Molecular Targeted Therapy / Q000379:methods*
D050256:Antimitotic Agents; D018797:Cell Cycle Proteins