- Liu M, Ren Y, Zhou Z, Yang J, Shi X, Cai Y, Arreola AX, Luo W, Fung KM, Xu C, Nipp RD, Bronze MS, Zheng L, Li YP, Houchen CW, Zhang Y, Li M. The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia. Cancer Cell. 2024 Mar 29:S1535-6108(24)00094-1. doi: 10.1016/j.ccell.2024.03.009. Epub ahead of print. PMID: 38608702.
New findings on cancer cachexia
Research reveals a previously unknown mechanism that triggers cachexia, a muscle weakness condition common in pancreatic cancer patients.
Translated from the original Italian version.
Overlap between cancer cells and macrophages
In a recent study, a group of researchers found that "crosstalk" between pancreatic cancer cells and macrophages is the first step in the onset of cachexia. Normally, macrophages protect the body from infection, but in this case, pancreatic cancer cells recruit them for a different action that leads to damage to the body.
This interaction in turn leads to an increased release of TWEAK (TNF-like weak inducer of apoptosis), a protein that is known for its role in cachexia by binding to receptors on the surface of muscle cells and triggering inflammation. This sequence triggers the development of cachexia.
"Cancer cachexia is a poorly researched disease for which there are no good treatments, and no nutritional support helps," said Professor Li. According to Professor Li, patients lose their appetite and lose weight quickly and are therefore weakened and much less able to tolerate aggressive treatment for pancreatic cancer. The significance of this study is that it demonstrates a mechanism underlying cachexia: "It is not the tumour cells or the macrophages alone that trigger the cachexia process, but the fact that they "communicate" with each other", added the Professor.
Tumour cachexia does not occur in all types of cancer. It is rare in breast or brain tumours, for example, but is more common in pancreatic cancer. The results of the study are important because if researchers can better understand how cachexia begins, they may be able to develop a way to stop the cascade of events.
According to the researchers, this study will open a therapeutic window to intervene and potentially stop or reduce cachexia so that patients have a better chance of fighting pancreatic cancer. The research group will try to develop a drug that may be able to block the interaction between cancer cells and macrophages.
Image credit: Cancer Cell
Towards an early diagnosis of pancreatic cancer
According to the authors, this is paradigm-shifting research as it represents a new way of understanding the development of cancer cachexia. The combination of pancreatic cancer and cancer cachexia significantly reduces the quality of life of those affected. If the effects of cachexia can be reduced, patients could have a better prognosis in the fight against pancreatic cancer, which today has a five-year survival rate of only 13 per cent and is the third most common cause of cancer-related death in the USA, for example.
Pancreatic cancer is notoriously difficult to detect at an early stage; in more than 80 per cent of patients, the disease is not diagnosed until the tumour is advanced and treatment options are limited. Professor Li's research not only provides a potential target for treatment, but may also contribute to earlier diagnosis of pancreatic cancer. Previous clinical studies have shown that people first lose fat and then muscle six to nine months before being diagnosed with pancreatic cancer.
"If a person loses more than five per cent of their body weight in a six-month period for no reason, that could be cause for concern," Professor Li said. "Perhaps the changes in a person's body composition could help doctors diagnose cancer at an earlier stage, before it has metastasised", Li suggested.