Potential reasons behind weight loss in advanced cancer uncovered

The study, which is part of the Cancer Research UK TRACERx programme and is published in Nature Medicine, found distinct patterns of genes that were much more likely to be found in the tumours of patients with cachexia, and could lead to a way to diagnose the condition before symptoms appear.

Researchers also found a high correlation with levels of GDF15 (a protein which other studies have previously linked with appetite and weight loss) in the blood. The team believe that by targeting this protein with treatment, they may be able to manage cachexia or prevent it completely.

Although involuntary weight loss and muscle wasting has long been linked with fatality, a biological reason for cachexia has eluded scientists. And although up to 80% of patients in an advanced stage of cancer experience some degree of cachexia, it remains complicated to diagnose and there are no globally approved therapies or treatments.

Dr Mariam Jamal-Hanjani (UCL Cancer Institute), 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.”

The researchers used a cutting-edge AI-assisted method to process hundreds of scans from patients who had relapsed after surgery and who had lost muscle and fat. The scans showed how much muscle and fat patients had in their abdomens.

Consequently, the team were able to identify patients with cachexia and carry out a comparison of patients with and without the condition at unprecedented detail.

The process also revealed a link between the distribution of fat at the time of diagnosis and survival – with lower levels of body fat at baseline being associated with poorer survival outcomes.

In the future, the researchers hope to build on this work by investigating if cachexia develops in some patients at later stages of disease, and they will examine the tumour and blood samples collected in TRACERx to explore how cancer metabolism and the immune system might play a role in cachexia.

They are also hoping to explore whether inhibiting GDF15 could reverse features of 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.

“The TRACERx researchers were able to explore these vast amounts of data with open minds and have come away with discoveries that have the potential to make real differences to people with cancer.

“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.”

Links

• Research in Nature Medicine
• Dr Mariam Jamal-Hanjani's academic profile
• UCL Cancer Institute
• UCL Medical Sciences
• The Francis Crick Institute
• CRUK

Image

• Credit: gorodenkoff on iStock

Media contact 

Poppy Danby 

E: p.danby [at] ucl.ac.uk