Predicting treatment response in bowel cancer
Original story from The Institute of Cancer Research.
Scientists have developed a tool that can predict how bowel cancer adapts to treatment – helping researchers to design new personalised drugs that will keep patients living well for longer.
A team from the Institute of Cancer Research (ICR; London, UK) and Queen Mary University of London (QMU; UK) have designed a new technology that uses evolutionary biology to measure and predict how cancer cells will evolve when they are exposed to a new treatment.
Bowel cancer is the fourth most common cancer in the UK. There are around 44,100 new bowel cancer cases in the UK every year, or around 120 every day. Most bowel cancers are treated with chemotherapies and these treatments haven’t changed in almost 50 years. Patients with late-stage disease typically die from drug resistance – when the cancer stops responding to treatment.
Drug resistance is caused by molecular changes in cancer cells that renders the treatment ineffective. Understanding exactly how this resistance develops will allow researchers design new and better drugs that target the mechanisms of resistance – ensuring cancer is kept at bay for longer. It will also allow clinicians to use existing drugs in the optimal way – altering doses if necessary.
“This treatment resistance is a long-standing problem that we are desperate to solve. Cancers may respond well for a while, but sadly then they usually become resistant and the drug stops working,” said Trevor Graham (ICR).
Combining existing blood cancer treatments in new ways
Thousands of patients with a common type of blood cancer could benefit from a new drug combination, while others could see their disease kept at bay for longer.
There are two routes that cancer cells can take to escape a drug’s action, but until now, it has been very hard to tell them apart. In research published in the journal Nature Communications, the team from the Centre for Evolution and Cancer at the ICR, funded by the Wellcome Trust and Cancer Research UK, tracked bowel cancer cells as they evolved resistance to chemotherapy.
Together with colleagues from QMU, the researchers used mathematical modeling to pinpoint when resistance to the drug developed. They could then determine whether resistance was caused by a rare genetic mutation in one cell that was copied as the cell divided, or whether there was a non-genetic change responsible.
The researchers have now turned their method, called EIRAs (Evolutionary Informed Resistance Assays), into a tool that can be adopted into the process of developing new medicines. By using EIRAS, they hope that new personalised drugs can be designed which target the route that a patients’ tumor has taken to evolve resistance.
The researchers are seeking commercial partners to further progress this work, as well as working with colleagues in the ICR’s Centre for Cancer Drug Discovery. A patent has been submitted for the technology, which the researchers believe could be used to support the development of a number of cancer drugs – they have already begun exploring its use for ovarian and breast cancer.
“By studying bowel cancer cells over time as we treat them with chemotherapy, we have been able to develop a machine learning technology that can unpick how and when these cells become resistant,” continued Graham. “We hope this information will allow us to design new, personalised drugs – ones that target these changes so that the cancer responds to treatment. We also believe we can use the technology to learn how to alter the dose of existing drugs, to keep them working for longer.
Morag Foreman (The Wellcome Trust) said, “Every cancer is unique and will not respond to treatments in the same way. Recognising how resistance develops on a case-by-case basis means we can tailor treatment plans for individuals to ensure they continue to be effective, adding another tool to help us better understand cancer as a disease.”
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