Almac scientists’ breakthrough could ‘stop cancer in its tracks’

Mathematicians worked during Lockdown with biologists at Queen’s University, Belfast in a creative approach to finding a novel way of treating cancer.

The research, published by the scientific group funded by Almac in Craigavon, has been shared online and may be the starting block for a new way of treating individual cancers.

The scientists identified nearly thousands of gene pairs that represent ‘Achilles Heels’ or cancer vulnerabilities in analysis of more than 700 different cancer models.

Mark Wappett Head of Bio-informatics at Almac Discovery explained: “With cancer, it is not like a bacteria or a virus. Cancer is your own cells going wrong essentially.

“If you have, for example, a lung cancer - all that is, is a group of lung cells which aren’t behaving like lung cells should. That’s what makes cancer difficult to treat because your body finds it very difficult differentiating cancer and the normal cells and so do the drugs. That is why they are so toxic.

“These ‘achilles heels’ have been found because cancer cells are full of these mutations and DNA and the effect of this is sometimes you can have a mutation in a cancer cell which makes the cancer very dependent on another gene,” said Mr Wappett who shared the example is BRCR mutations or the breast cancer gene. There are two different genes that have been found to impact a person’s chances of developing breast cancer.

“If you find the gene in the gene pair you can develop a drug against it. Then you can selectively kill all the cancer cells and you won’t have the side effects or toxicity.”

Not only will this ability to find the gene pairs for many cancers but it could stop cancer in its tracks and propose new targets for drug development. These drugs could even be used to combat cancers that do not respond to the current standard treatments.

The work was carried out by Mr Wappett in collaboration with the Overton and McDade groups in the Patrick G Johnston Centre for Cancer Research (PGJCCR) at Queen’s University Belfast and the Department of Biochemistry at Vanderbilt University, USA.

Work had started on the project about five years ago. “It has been knocking around for a couple of years but, during Lockdown, we managed to crack it,” said Mr Wappett.

Pivotal to the research is a completely new computational method for discovering cancer synthetic lethality from clustered regularly interspaced short palindromic repeats (CRISPR) and gene expression data using a website called ‘SynLeGG’. This site analyses large and complex datasets to identify changes in genes that occur in certain cancers that may make them more addicted to other similar genes and therefore susceptible to treatments targeting these partners. It was published today (17 May) in the journal Nucleic Acids Research and can be accessed here.

Mr Wappett said: “Synthetic Lethality with Genetics and Genomics, or SynLeGG for short, provides the wider scientific community access to key datasets generated by cutting edge molecular biology technologies, such as CRISPR, and a toolkit with which to analyse this data. Ultimately we hope that by increasing the reach of this data we can expedite more targeted and effective cancer treatments.”

Dr Ian Overton, Senior Lecturer at the PGJCCR explains: “Understanding the molecular fingerprints of cancer can pinpoint ways to target drugs precisely to those patients where they will be most effective. Our work makes a step towards more effective and personalised cancer treatments, ultimately saving lives.

“We make our results available on the SynLeGG web server, opening a window to share these rich resources with researchers across the scientific community – in order to accelerate progress in cancer research.”

Dr Simon McDade, Senior Lecturer from the PGJCCR said: “We anticipate that this resource will seed detailed investigation of a number of specific vulnerabilities we have identified, ultimately identifying novel treatment strategies that will translate into significant benefits for cancer patients in the long term.”

The results of MultiSEp are available at www.overton-lab.uk/synlegg.

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