UK’s ICR to Tackle Treatment-Resistant Cancers with “Darwinian” Drug

Cancer cells

The Institute of Cancer Research (ICR) in London, UK, is investing an initial £75 million to create a global center in what it is calling anti-evolution therapies for cancer. The evolution, in this case, refers to cancer’s ability to adapt and evolve to resist cancer drugs. They are dubbing it the world’s first “Darwinian” drug development program.

“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,” stated Paul Workman, chief executive officer of the ICR. “At the ICR, we are changing the entire way we think about cancer, to focus on understanding, anticipating and overcoming cancer evolution.”

The new program will focus on two broad approaches. The first is called “evolutionary herding.” Since many of the mechanisms of cancer drug resistance are known, the first step is choosing an initial treatment that forces the tumors to adapt in specific ways that make them susceptible to a second drug. This next evolutionary step would be a dead end.

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The second pathway is to look at a possible new class of drugs that attack cancer cells’ ability to evolve and develop drug resistance. The ICR is specifically looking at molecules that block APOBEC proteins, which are in the immune system. When misregulated they are a common source of mutation in cancers. They hope that APOBEC inhibitors, once developed, could be prescribed alongside targeted cancer therapies to hold off cancer from evolving for a longer period.

Olivia Rossanese will be head of biology in the Cancer Research UK Cancer Therapeutics Unit within the Division of Cancer Therapeutics. “More and more cancer patients are living longer and with many fewer side effects through new targeted cancer treatments. But unfortunately, we’re also seeing that cancer can become resistant very quickly to new drugs—and this is the greatest challenge we face. Within the Centre for Cancer Drug Discovery, we plan to deliver a drug discovery program that is wholly focused on meeting the challenge of cancer evolution and drug resistance through completely new ways of attacking the disease.”

The ICR is looking for another £15 million from philanthropic donations to finish the new building and buy state-of-the-art instrumentation and computational technology. Several projects internally will include using artificial intelligence (AI) to “herd” cancer, developing the first anti-evolution cancer drug, and discovering multi-drug combinations that block several different cancer genes or that stimulate the immune system.

Workman stated, “If we can raise a further £15 million to deliver our new Centre for Cancer Drug Discovery, we can bring together under one roof experts in cancer therapeutics alongside others studying evolution in animals, cells and individual patients to create a new generation of cancer treatments.”

Andrea Sottoriva will act as Deputy Director of Cancer Evolution. She stated, “Artificial intelligence and mathematical predictive methods have huge potential to get inside cancer’s head and predict what it is going to do next and how it will respond to new treatments.”

ICR researchers have already presented evidence that combinations of targeted treatments have potential for preventing cancer resistance, which is an approach seen in HIV and tuberculosis, as well. They have tested a three-drug combination to block drug resistance in bowel cancer.

“This ‘Darwinian’ approach to drug discovery gives us the best chance yet of defeating cancer, because we will be able to predict what cancer is going to do next and get one step ahead,” Rossanese stated.

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