Scientists uncover clues behind drug resistance in bowel cancer

Scientists have discovered clues that may explain why some treatments stop working for people with bowel cancer—causing about 16,800 deaths in the U.K. every year.

The study, led by researchers at The Institute of Cancer Research, London, could help clinicians make better use of current treatments and develop more targeted therapies for bowel cancer in the future.

In an article published in the journal Cancer Research, the team studied bowel cancer organoids, tiny lab-grown versions of human organs designed to model how cancer cells behave in our bodies.

Building up a picture of resistance

The researchers looked at two sets of bowel cancer organoids with different genetic makeups and how they responded to four cancer treatments given in different sequences over 45-day periods. This helped build up a detailed picture of their evolution and behavior over time.

The study found that cancer cells can develop a “memory,” through switching on and off certain processes in the cell, known as “epigenetic changes.” Cells can “remember” the form and appearance they need to adopt to survive harsh conditions, such as being bombarded by cancer drugs. The resulting survival mode “memories” are then passed on when cancer cells grow and divide, resulting in a cluster of drug-resistant cancer cells.

Dr. Erica Oliveira, senior scientific officer at The Institute of Cancer Research, London, and one of the lead authors of the paper, said, “We have known for some time now that drug resistance isn’t simply caused by further mutations in the DNA of cancer cells.

“Our work shows the additional role epigenetic changes play in giving cancer cells the ability to adapt to their surroundings, unfortunately resulting in certain cancer treatments becoming less effective over time.

“We look forward to further studying these processes to see if we can target them directly as a strategy for beating bowel cancer.”

Designing more targeted treatments

Cancer is a complex disease. Existing treatments don’t necessarily work for everyone, and all cancers are at risk of evolving and becoming resistant to treatments over time. This, in part, is down to changes in the genetic instructions inside the DNA of every cell.

Increasingly, scientists are building a better understanding of the other processes involved in driving drug resistance. The findings from this multi-year research project give us one of the most detailed studies to date about how drug resistance can develop in bowel cancer.

Professor Andrea Sottoriva, Professor of Cancer Genomics and Evolution, Head of the Center for Computational Biology at Human Technopole, and formerly The Institute of Cancer Research, London, said, “Our findings could potentially be used to inform how we treat bowel cancer in a more targeted way.

“If we can test a sample from a patient with bowel cancer and confirm their cancer cells have survival ‘memories’ and are at risk of developing resistance, we could potentially change the order that current drugs are given, or develop new therapies designed to make cancer cells ‘forget’ how to survive.”

Dr. Iain Foulkes, executive director of research and innovation at Cancer Research UK, said, “For over 100 years, our scientists have been working to beat bowel cancer. We were pleased to fund this work looking at how bowel cancer cells change over time in response to different cancer therapies.

“Discoveries like this could potentially help us anticipate how a person’s cancer might evolve, allowing us to design more targeted ways of treating the disease, whether that’s making use of current drugs or designing new ones.”