Scientists step closer to learning why advanced cancer causes sudden weight loss

A gene, called GDF15, has been found to be associated with cachexia.
Scientists move one step closer towards understanding the devastating loss of fat and muscle during cancer (Chris Radburn/PA)
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Nilima Marshall12 April 2023

Scientists believe they are a step closer to understanding more about sudden and “devastating” weight loss that occurs in patients with advanced cancer.

Researchers in the UK have found a gene, called GDF15, to be associated with cachexia – a complex process that leads to the sudden loss of appetite, fat and muscle in 80% of cancer patients in the late stages of the disease.

It is thought to be the primary cause of death in 20–30% of cancer patients.

The team said its findings from the TRACERx study, published in Nature Medicine, could help diagnose the condition before symptoms appear.

Dr Mariam Jamal-Hanjani, clinical associate professor at University College London’s Cancer Institute and lead researcher on the study, said: “A biological understanding of this devastating condition has long eluded researchers, but the incredible investment and in-depth sample and data collection in TRACERx has allowed us to begin to make discoveries in cachexia.

“We are particularly excited about trying to find alterations in the cancer or blood that can help identify which patients are at risk of developing cachexia in the future so that we can intervene before this happens.”

Findings like this will build up the toolkit we need to fight it

Prof Ketan Patel

Funded by Cancer Research UK, the £14 million TRACERx study used techniques involving artificial intelligence to process hundreds of scans from patients who had relapsed after surgery and who had lost muscle and fat in their abdomens.

The researchers were able to identify those patients with cachexia.

This condition can often be hard to diagnose because there is no single screening tool that is effective in detecting cachexia.

As part of the next steps, the researchers will investigate how cancer metabolism and the immune system might play a role in cachexia.

Professor Ketan Patel, chief scientist at Cancer Research UK said: “This study is a powerful example of what can be achieved when researchers have the space and time to look closely into what happens to our bodies when we have cancer.”

He added: “Cachexia is a condition that’s devastating to patients – it leads to poor quality of life, impairs the ability to tolerate treatment and contributes to mortality.

“Findings like this will build up the toolkit we need to fight it.”

Professor Charles Swanton, of the Francis Crick Institute and Cancer Research UK chief clinician, who is the lead on the TRACERx programme, said: “TRACERx recognises that cancer is not static and the way we treat patients shouldn’t be either.

“This approach that we’ve been able to take – following patients through their cancer journey and looking at how cancer interacts with the whole body has allowed us to interrogate this condition in a way that hasn’t been possible before.”

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