Mitosis, genome stability and cancer chemotherapy
|3 July 2015
|15:00 - 16:00
|What is it:
|Faculty of Life Sciences
|Who is it for:
|University staff, Current University students
|Prof Stephen Taylor
The next seminar in the ‘Celebrating Research Success in FLS’ series will be given by Prof Stephen Taylor, who is a member of the Cell and Cancer Biology Research Theme.
Antimitotic drugs, including the microtubule stabilizer taxol, are front-line chemotherapy agents used to treat breast, ovarian and prostate cancer. However these drugs a far from perfect; we can’t predict which tumours will respond, we don’t know how resistance develops, plus toxicity can be a problem. To address these limitations, a new generation of inhibitors that disrupt mitosis without affecting microtubule dynamics are being developed, yielding excellent drugs targeting mitotic kinesins and mitotic kinases. However these drugs have thus far not been impressive in the clinic, further highlighting our limited understanding of the mechanisms that dictate cell fate in response to mitotic disruption. Following a genome-wide siRNA screen we discovered that the oncogenic transcription factor MYC is a taxol sensitizer. Using time-lapse imaging to correlate mitotic behaviour with cell fate, we show that MYC sensitizes cells to mitotic blockers and agents that accelerate mitotic progression. Using gene expression profiling and functional experiments we delineated a MYC-dependent apoptotic sub-network required for death in mitosis and post-mitotic apoptosis. Experiments in mice show that MYC sensitizes intestinal epithelial cells taxol-induced apoptosis, and gene expression analysis of breast cancers suggests that the mechanism influences tumour responses to chemotherapy. Moving forward, we hope that these results will open up opportunities for biomarkers and combination therapies that could enhance both traditional and second-generation antimitotic agents.
Prof Stephen Taylor
Organisation: Faculty of Life Sciences
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building