A gene could be behind why some late stage cancer patients experience sudden loss of weight, appetite, and muscle, researchers have announced.
The study, part of the Cancer Research UK TRACERx programme and published in Nature Medicine, found patients with cachexia were more likely to have distinct patterns of genes in their tumours.
The research team also spotted a high correlation with levels of the protein GDF15 in the blood, which other studies had previously linked with appetite and weight loss.
The TRACERx researchers say they hope their discovery could help them find a way to manage cachexia or even stop it.
Professor Charles Swanton, lead of 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.”
TRACERx, a £14 million study funded by Cancer Research UK and carried out at the Francis Crick Institute, with University College London (UCL) and collaborators at Mass General Brigham and Harvard Medical School, explores the evolution of cancer in real time, following patients with non-small cell lung cancer from diagnosis to either relapse or cure after surgery.
Although clinicians have long known about the link between cachexia and up to 80% of patients with advanced cancer, there was no biological understanding as to why it happened.
The researchers used an artificial intelligence (AI) assisted method to process hundreds of scans from patients who had relapsed after surgery and who had lost muscle and fat, identifying those patients with cachexia and comparing them with patients with and without the condition.
They found 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.
The team now hopes to investigate if cachexia develops in some patients at later stages of disease and to explore if inhibiting GDF15 could reverse features of cachexia.
Professor Ketan Patel, chief scientist at Cancer Research UK, said: “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.”
Al-Sawaf O, Weiss J, Skrzypski M et al. Body composition and lung cancer-associated cachexia in TRACERx. Nature Medicine 12 April 2023
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