Joining forces with Novartis to advance novel cancer therapeutics

26th October 2019

The Beatson Drug Discovery Unit (DDU) has recently entered into a collaboration with Novartis to progress its ground-breaking work on the development of KRAS inhibitors.

KRAS belongs to a family of proteins commonly mutated in cancer. The genetic instructions for RAS proteins are altered in 30% of all cancers, and mutations are even more frequent in lung, colorectal and pancreatic cancer. These changes drive KRAS to be constantly active – similar to a stuck key on a keyboard - instructing cells to divide uncontrollably and produce more and more cells. In some cancer types, KRAS mutations are particularly aggressive and are linked to a higher number of cancer deaths.

For many decades, it has been difficult to find a direct pharmacological approach to target RAS proteins and they have been labelled 'undruggable'. While targeting direct binding with KRAS, the Beatson DDU has managed a significant breakthrough building on their leading expertise in fragment and structure based drug design. This drug development strategy screens a library of very small molecules called fragments and aims to identify binding pockets to target on the protein that will enable us to stop KRAS functioning in cancer patients. Using X-ray crystallography and computational chemistry, our chemists aim to grow these fragments into powerful and potentially effective drugs that can be used safely in clinical trials.

Through a negotiation with Sixth Element Capital, the fund manager for the Cancer Research Technology Pioneer Fund (CPF), Novartis will work together with the Beatson DDU to develop KRAS inhibitors further and has the option to exclusively licence certain drugs arising from this partnership. Novartis is making an upfront payment to CPF but will also contribute to funding ongoing research in the DDU for the duration of the collaboration, alongside continued support from CPF and CRUK. This will bring additional technical expertise and resources to the project, accelerating the delivery of potential drugs to benefit cancer patients.

Click here to read more from Cancer Research UK.

Payam Gammage joins the Beatson Institute

14th August 2019

Gammage head 2020 067The Beatson Institute is delighted to welcome Dr Payam Gammage as a Junior Group Leader. Payam joins the Institute from the MRC Mitochondrial Biology Unit, University of Cambridge where he developed methods to manipulate mitochondrial DNA and applied them to study mitochondrial dysfunction in cell and animal models.

Mutations of mitochondrial DNA are found in the majority of all solid tumours, often at levels that should be capable of impairing the normal function of the mitochondria, which are described as the 'powerhouse' of the cell. Mitochondrial dysfunction in cancer is associated with a switch in the cell's energy metabolism from oxidative phosphorylation to glycolysis, however the contribution of mtDNA mutations to this process is not yet clear. Payam's group here at the Beatson will be investigating the role of the mitochondrial genome in human cancer. With the eventual aim of identifying new therapies for cancers bearing mutations in their mitochondrial DNA, the lab is particularly interested in studying their role in carcinogenesis as well as tumour formation and metastasis.

Payam has said 'I am genuinely thrilled to be joining the CRUK Beatson Institute. This place offers an amazing blend of expertise, resources and friendly, collaborative environment that it's fantastic to become a part of'

Julia Cordero awarded Pioneer Award

23rd May 2019

The Institute of Cancer Science’s Dr Julia Cordero has been awarded a Cancer Research UK Pioneer Award. These awards fund innovative, higher-risk ideas that could revolutionise our understanding of cancer.

Julia’s project will use fruit flies as a model system to study cancer-driven behavioural changes. These behavioural changes specifically relate to sleep disturbances and changes in feeding/eating habits. Disturbances to both of these are often experienced by cancer patients.

This is something that needs to be addressed, not only because these issues greatly affect a person’s quality of life, but also because these disturbances can actually affect how well the tumour responds to treatment and therefore how successful the cancer treatment is. So the potential benefit of addressing these behavioural changes is two-pronged: improving quality of life by improving sleep and nutrition, but also improving the chance of successful treatment.Cordero Julia

‘There have been a lot of correlational studies on this, but as of now there is very little science,’ Julia said. This is where Julia’s Pioneer Award project steps in. The project aims to dig down into the specific molecular mechanisms underlying how intestinal tumours affect sleeping and eating behaviours.

It is already known that the intestine controls cellular signalling pathways that affect other parts of the body, including the brain. This project will look into how they do this and how this leads to changes in sleeping and eating. The hypothesis is that tumours actively influence brain function.

The ultimate goal of the work is to develop therapies specifically aimed at addressing these sleeping and eating disturbances in cancer patients. Such therapies might include small molecules or peptides, some of which are already in use for other conditions.

Click here to read more about Julia’s research.



Making more proteins for drug discovery research

1st May 2019

Beatson Institute researchers have unravelled a new way to maximise the production of important cancer-related proteins for study in the laboratory.  This work, led by Dr Chris Gray of the Institute’s Drug Discovery Programme, has demonstrated that subtle changes to the genetic instructions given to bacterial protein factories can dramatically improve the recovery of high-quality proteins. 

The work has been published in PLoS One.  

These findings refine and optimise current recombinant technologies, used globally for the production of proteins for the laboratory and the clinic.  As a consequence of this discovery, larger amounts of key reagents can be delivered to our drug discovery programmes, accelerating the development of new therapies.

Click here to read more about the Drug Discovery Programme.

Ed Roberts joins the Beatson Institute

17th April 2019

Roberts Ed March 2019The Beatson Institute is very pleased to welcome Dr Ed Roberts as a new Junior Group Leader. Ed joins the Institute from UCSF, where he studied a class of immune cell called migratory dendritic cells and the role they play in the body’s response to cancer, and specifically how these cells communicate with the lymph nodes.
This immune response underpins a type of cancer treatment called immunotherapy, in which the body’s own immune system is used to fight cancer. Despite great successes with immunotherapy, it only works in a subset of patients. Ed’s group here at the Beatson will be investigating how the immune response could be boosted, with the aim of making immunotherapy successful for more patients.

Ed has said 'It’s been really great settling into an incredibly friendly and collaborative environment that has such exciting science going on. Everyone has been incredibly helpful with everything which has made the process of moving in much less painful than I had expected!'

Two recent major projects

17th April 2019

Bowel Cancer UKBeatson Institue Director Owen Sansom has been interviewed by Bowel Cancer UK about an exciting project he is leading that aims to improve outcomes for bowel cancer patients. Click here to read the interview.

Another major project Owen is involved in - which aims to find out why different gene faults only cause cancer in particular parts of the body - has been covered by Cancer Research UK's blog.


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