AICR funded discovery could be key to a new generation of targeted cancer therapies
With funding from AICR, Professor Robert Cross and his team at the University of Warwick Medical School have discovered a critical point of failure in the microscopic transport system that operates inside every cell in the human body.
Professor Cross told AICR “Our findings help us to understand how some existing cancer drugs actually work. This in turn should lead to the development of new generations of better, more effective drugs for patients.”
The study, published this week in Nature Communications, explains that this tiny, molecular so called ‘railway’ system is a key target for cancer drugs and reveals how better drugs might be made.
The tracks of this ‘railway’ are tiny tubes, called microtubules, 1000 times thinner than a human hair.
It has been known for some time that microtubules have a single seam that zips the structure together along its length, but the function of this seam has evaded scientists until now. Maybe somewhat unsurprisingly, the findings show that this seam is the weakest point. If the seam cracks and splits, the microtubule dissolves.
Microtubules are a validated target for cancer therapy drugs. For example Taxol™, used in breast cancer therapy, binds to microtubules and stops the microtubule from dissolving. This means the microtubule tracks cannot remodel themselves prior to cell division, which prevents the cells dividing, thus arresting the growth of cells including those forming cancerous tumours.
By building microtubules with extra seams in the laboratory, and examining their stability using video microscopes, the researchers found that the more seams the microtubule has, the more unstable it becomes.
This research dramatically alters our thinking on how the microtubule system works and the hunt is now on for factors inside the cell that influence the stability of microtubule seams.
Professor Robert Cross, Head of the research team at Warwick Medical School, explained, “It is clear that any new drugs aiming to stabilize or destabilize microtubules must target the microtubule seam. We expect this work to lead us to a better understanding of the way microtubules are regulated in cells and why this sometimes goes wrong, such as in development of cancer.“
Dr Lara Bennett, Science Communication Manager at AICR, said “Now that researchers know the seam is the ‘Achilles heal’ of the microtubule tracks, new drugs can be developed to target this specific area. This is a great example of the importance of lab based research which shines the light on new avenues of research which can lead to better treatments for patients in the future’
The research was funded by the Association for International Cancer Research (AICR) and Marie Curie Cancer Care.