Cancer hijacks our body’s cells to make them grow and multiply too fast. Every treatment aims to stop this process or slow it down. But what if we could do the opposite: speed up cancer cells so much that they destroy themselves?
Researchers hope to upend traditional approaches to cancer treatments by hyperactivating cancer cells and pushing them into overdrive. Rewire-Can, an international collaboration centred at University College London, aims to create an entirely new form of cancer treatment.
Their research focuses on bowel cancer, which has been rising among the under-50s and is the fourth most common cancer in the UK, with about 44,100 new cases a year. As well as trying to make cancer cells explode themselves, the research is trying to reprogram treatment-resistant tumours to become treatable again.
The project is part of Cancer Research UK’s Cancer Grand Challenges, which funds research on cancer’s unsolved issues, and will get up to £20m over five years from CRUK and the National Cancer Institute, with help from the Bowelbabe Fund, set up in honour of Deborah James, who created the You, Me and the Big C podcast.
Cancer research has been transformed in the last 10 years by technology that can analyse individual cells. Chris Tape, professor of cell communication at UCL, said that has enabled researchers to build an anatomy of tumours, establishing that there are different types of cancer cell states with different roles – a perversion of normal human tissue.
“Cancers are essentially a horrible extension of healthy biology,” Tape said. “They don’t do new things, they just reuse processes that are normally helpful for things like tissue growth and wound healing.”
When chemotherapy and radiotherapy attack cancer cells, the tumours go into a slow-growing state, wait for the treatment to pass then regrow. The Rewire-Can approach intends to turn this advantage on its head, even when cancers reach a stage in which they become untreatable.
Bart Vanhaesebroeck, Rewire-Can’s lead researcher and professor of cell signalling at the UCL Cancer Institute, calls it “lethal hyperactivation”, explaining: “If a cancer cell is a balloon full of air, what traditional medicine has been doing is to squeeze the air out of the balloon so it goes a bit floppy. But when the time is right, it can come back. But if you put just 5% more air into a fully blown balloon, it pops. And we now have unpublished data that show this is possible.”
Vanhaesebroeck has spent much of his career working on inhibitor drugs, which slow down cancer by turning off its “growth switch”. But when he felt he had reached the limits of inhibitors, he began thinking about whether the inverse idea, an activator, might also work. The reaction was sceptical, but AstraZeneca funded research that led to a paper in Nature in 2023 that showed activators had potential.
“I have been 10 years in the desert with this activator concept,” Vanhaesebroeck said. “I nearly lost my job. But suddenly people have [accepted the idea] and patients are maybe the strongest advocates for them .”
The team now has a platform to make potential new drugs and to examine cells in the laboratory, but moving from concept to new drug compounds will take “two to three years”, Vanhaesebroeck said.
Part of the problem in cancer drug development is that patients are often very different, Tape said, and promising drugs fall by the wayside. Rewire-Can is taking this head-on by screening drug candidates on 100 samples taken from patients’ healthy and cancerous tissue.
These samples are being used to create organoids – miniature versions of colons in a Petri dish – which can be exposed to potential new drug compounds to see how they react. It means they can test 192 combinations of activator drug per patient.
Vanhaesebroeck said they had chosen bowel cancer because it is easier to grow tumours in the lab from patient samples. “That is not the case for all tumours, but our methods would be applicable to other tumours.”
Dr David Scott, director of Cancer Grand Challenges, said Rewire-Can’s unconventional approach “could open up an entirely new class of cancer treatment”.
Photograph by Vladislav Stepanov
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