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We may have a way to out compete cancer’s ability to evolve

Image credit: AmeVia, Flickr CC BY-NC-SA 2.0

Treating cancer is not an easy task. But, as discussed in the first of this two-part story, we do have some powerful weapons to use against it. However, one essential question remains: How can we outsmart cancer in what seems like an eternal arms race?

In part one, we compared cancer to the mythical beast hydra, a creature with many heads, requiring a range of weapons to defeat it. We can use sword, fire and poison to try and bring the beast down, but the writhing heads regrow and seem to grow back stronger with every blow against them. Cancer is Darwinian. It evolves. Every time we develop a new treatment to attack cancer, it adapts to survive.

Anti-evolution

To tackle this problem directly, the Institute of Cancer Research in London is now building the world’s first “Darwinian” cancer drug programme in a dedicated state-of-the-art centre for drug discovery. The aim is to create a global centre of expertise across several disciplines. To hit cancer where it hurts, the ICR is planning to bring together a host of different minds from a variety of fields. The approach is to focus on “anti-evolution” therapies to outsmart cancer and stop it from adapting to treatment.

Professor Paul Workman, Chief Executive of the ICR, said in a press release: “Cancer’s ability to adapt, evolve and become drug resistant is the cause of the vast majority of deaths from the disease and the biggest challenge we face in overcoming it. At the ICR, we are changing the entire way we think about cancer, to focus on understanding, anticipating and overcoming cancer evolution. We will create exciting new ways of meeting the challenge of cancer evolution head on, by blocking the entire process of evolutionary diversity, using AI and maths to herd cancer into more treatable forms, and tackling cancer with multi-drug combinations as used successfully against HIV and tuberculosis.”

Charles Darwin - evolution becomes a target for cancer research

Halting evolution

But how could we possibly put a halt to evolution? Scientists believe one possible way will emerge from studying a group of proteins found in our cells called APOBEC proteins. APOBEC proteins are used by cells of our immune system to adapt to the diverse, ever changing invaders in the form of viruses and bacteria. Our immune system can not only recognize these invaders but also memorize them and develop specific defences to repel an attack. To do this the immune system needs to evolve and adapt to keep ahead of the invaders, which is a key function of APOBEC proteins.

It turns out that APOBEC proteins also help cancers to evolve and adapt by driving genetic mutations that allow the disease to become resistant to therapies. The hope is that by understanding more about how APOBEC proteins do this, we will be able to develop drugs that block them. Ultimately, these could be given alongside other treatments, stopping the cancer from evolving and enhancing the efficacy of current drugs.

Understanding evolution

These developments and big ideas are exciting, but they didn’t come from nowhere. In 2013, a multinational team led by the Wellcome Trust Sanger Institute published an article in the science journal Nature revealing a set of 21 mutational signatures in the genomes of 30 different cancer types. These mutational signatures revealed clues into the root biological cause for the way the different mutations occurred in cancer over time. One cause, which was driving two of the signatures found in more than half of the 30 cancer types studied, was overactive forms of the APOBEC proteins. This was the key piece of the puzzle that revealed APOBEC proteins as contributors to how cancer evolves and adapts.

Professor Vyacheslav Filichev

R-evolutionary research

In 2016, our supporters helped to fund Professor Vyacheslav Filichev’s at Massey University, New Zealand, to study one of the APOBEC proteins and its potential to stop cancer evolution. Part of his work aims to advance the understanding of how APOBEC proteins work in a healthy cell. By understanding the basics behind how APOBEC proteins allow cells to evolve, we will speed up the development of treatments targeting cancer evolution and drug resistance. In February 2019, Professor Filichev and his team published data showing how they have laid the initial groundwork for the development of drugs that can block APOBEC in cancer.

Dr Helen Rippon, Chief Executive of Worldwide Cancer Research, said: “I remember Professor Filichev’s project creating quite a buzz when it was presented to our Scientific Advisory Committee. This global group of cancer research experts saw how exciting and new the possibility was of developing drugs to put the brakes on cancer evolution. This was very innovative 4 years ago and it’s fantastic to see that it has now gathered substantial investment from larger funders.”

APOBEC blockers and the large investment shown by others into their discovery and development highlights how relevant our philosophy is. With the help of you, our supporters, we are able to provide seed funding for ground-breaking and innovative research that is essential for the development of new approaches to treatment. This outside the box thinking is immensely important in making the discoveries that can revolutionise our understanding of cancer and open up new avenues of research. We believe that this is the way to go if we want to live in a world where no life is cut short by cancer.

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