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Outsmarting cancer – staying one step ahead of drug resistance


Cancer drug resistance is one of the biggest challenges of 21st century medicine – and a challenge that our researchers are facing up to. Rose Wu introduces how some of our researchers are aiming to outsmart cancer by tackling drug resistance.

Posted on 27 June, 2018 by Rose Wu

Mixture of pills

Mixture of pills. Source Pixabay (CC 0)

Our genetics help to determine the way we look, the way we act (are you an introvert or an extrovert?), how good we are at sport, art or music, if we like or can’t stand spicy food, and whether in the future we might get arthritis or diabetes.

Our genetic profile is unique to each and every one of us.

Tumours are similarly unique – each with their own individual genetic profile which influences how they behave, spread, and their ability to survive.

And in the same way that we change as we age, cancers adapt and change over time, evolving to take on new genetic changes, and developing new characteristics.

At The Institute of Cancer Research, London, we’ve put a spotlight on the ability of tumour cells to evolve, picking up genetic and other changes to develop cancer drug resistance, as our biggest challenge.

Our biologists, chemists, big data specialists and clinicians are working together to discover innovative treatments to overcome cancers’ resistance to treatment – and save more lives.

At the ICR, we’ve been improving the lives of cancer patients worldwide for over 100 years. Our researchers are developing new ways to combat cancer drug resistance, and to find better treatments that will ultimately save lives.

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Detecting and tracking the evolution of cancer cells

For example, Dr Marco Gerlinger is a team leader in the Centre for Evolution and Cancer at the ICR – an internationally leading centre of its type, where our researchers are applying Charles Darwin’s principle of natural selection to cancer research.

Dr Gerlinger has developed new tools to detect and track the evolution of cancer cells within a tumour. His team is particularly interested in gastrointestinal cancers, looking at how the genetic landscape of a tumour changes over time, and how these genetic and molecular changes drive resistance.

Dr Gerlinger’s team is researching ways to target these genes, to identify ways in which evolution can be stopped, reversed or targeted with new drugs.

Using big data in the fight against cancer

Computational approaches are increasingly allowing us to share and integrate diverse sets of data, often referred to as ‘Big Data’. Big Data gives us the potential to uncover knowledge that could not be observed by working on smaller, individual subsets of data.

Here at the ICR, we believe that using Big Data effectively will help us meet the challenge of drug resistance.

Dr Bissan Al-Lazikani’s Computational Biology and Chemogenomics Team develops tools that help drug discovery scientists process large amounts of data obtained from research. To give you an idea of the scale, the ICR’s scientific database about cancer, canSAR, contains more than 10 billion data points!

With the incredible surge in data comes a range of challenges that need to be addressed in order for us to use it to its greatest potential. The ICR is also working to raise awareness of how academic organisations can better work together – and with Government and industry – to capitalise on the promise of Big Data.

Disrupting cancer signalling networks

Cancer cells use hugely complex networks of signalling molecules to drive their growth and spread. If we block one signalling molecule, they can often find ways around it by using other parts of the network instead.

Our researchers are exploring the ‘social’ characteristics of cancer-causing proteins, finding the nodes in these networks to work out which parts of these networks we might target with new drugs, to strip cancer cells of their resilience and make it harder for them to survive.

Professor Keith Jones, Team Leader in Medicinal Chemistry, leads much of the ICR’s work to design and synthesise new compounds to inhibit the behaviours of cancer cells. He notes:

“Even as our approach to fighting cancer has become more sophisticated, cancer cells have demonstrated their resilience through increasing drug resistance.”

One recent breakthrough has been the team’s discovery of a molecule that can block HSF1 – a protein which activates under stress to drive cancer cells to make copies of themselves.

Around 200,000 chemicals were tested to narrow down the compounds that could block HSF1’s activity, and the most promising of these further refined through changes to their structure to increase their potency.

HSF1 has already been shown to be a promising target for myeloma, a cancer of white blood cells made in the bone marrow. The next step will be to test this potential new drug further through clinical trials.

In the future, HSF1-targeting drugs might be useful treatments for a range of cancer types, including hard-to-treat forms of ovarian cancer.

Help us to outsmart cancer

Adopting a multi-pronged approach, our researchers are ever finding new ways to understand how cancer cells develop drug resistance – and how we can outsmart their ability to do so.

With our supporters help, we can continue to push new techniques and develop new strategies to help defeat cancer for patients and their families.

You can learn more about the ICR and our cancer research discoveries, by signing up to our bi-annual e-newsletter, Search. In it, you can read about our latest research, our brilliant fundraisers and opportunities to support our work so that we can continue to defeat cancer.


Marco Gerlinger genetics CanSAR Bissan Al-Lazikani big data Keith Jones drug resistance informatics
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