One sort of fundamental science carried out here at The Institute of Cancer Research is structural biology, a discipline that in cancer research seeks to understand the shapes of proteins. Our scientists zoom in to tiny measurements – down to just a few ten-billionths of a metre – seeking to build incredibly detailed pictures of cancer-driving proteins.
Working closely with researchers in other disciplines, the aim is to design and make molecules that will block these proteins in highly specific ways, and eventually lead to clinical trials of new drugs based on these molecules.
A great example of cutting-edge structural biology was published last week by researchers in our Division of Structural Biology, who worked closely with the Medical Research Council Laboratory of Molecular Biology in Cambridge to pioneer an exciting microscopy technique – called electron cryo-microscopy – to visualise a cancer drug target called the proteasome complex at –180°C.
The current standard method for similar studies, X-ray crystallography, does not work for studies of all protein complexes – because of the technical challenges involved in generating the necessary copies of proteins, and coaxing them into highly ordered crystal structures. But the new study, published in Nature Communications, could aid in future efforts to design drugs that target this and other protein complexes guided by this latest technology.
New to nature
Other fascinating examples of ICR-led studies in structural biology over the past 18 months have included one which mapped another crucial protein complex called the APC/C, and an important new insight into DNA repair. Another discovered a new family of proteins which could be targeted by cancer drugs – and yet another discovered a new natural structure in protein folding. This ‘helix of a helix’ structure had not previously been found anywhere else in nature.
We are the top-rated higher education institution in the UK according to REF2014, the definitive national measure of research quality. And it is our ability to combine world-leading basic science with equally high-quality translational and clinical research which is the key to our success.
Two examples of ongoing research programmes help illustrate the importance of structural biology in finding new treatments: the development of Hsp90 inhibitors, now undergoing clinical trials thanks in part to earlier studies at the ICR, and those mapping studies of the APC/C complex, which have helped researchers in our Division of Breast Cancer Research in their aim to find drugs which might selectively target cancer cells in a new way, via the APC/C.
But the strength of basic research lies not only in its immediate impact – it can take many years for a discovery to lead to a new treatment – but also in telling us something completely new, making a fundamental discovery about cancer that was not previously known.
As Professor Workman says in his blog, fundamental cancer research is crucial because it leads to incremental and sometimes spectacular advances in our understanding of disease – an understanding which can often sow the seeds for advances that benefit patients.