Cachexia Research

Cachexia is a metabolic disorder that has been increasingly  focused upon in studies and clinical trials over the last decade. Although the understanding of this condition has improved considerably, lack of consensus among the medical fraternity on the classification, diagnostic criteria, and treatment approaches for cachexia has hindered meaningful progress in clinical trials.

Although largely overlooked by physicians in the past, cachexia is now viewed by scientists as a distinct condition which is treatable with the right kind of approach.

Basic cachexia research has helped to achieve better understanding of the inflammatory and metabolic factors that cause this condition. This in turn has helped researchers to find many drug targets for testing. However, a couple of major clinical trials in the recent years failed to give positive results, raising concerns about the potential loss of funding for cachexia research from the pharmaceutical industry.

Cachexia researchers also raise concerns about lack of adequate human data and samples for clinical testing. The need of the hour is more studies that track the progress of cachexia patients in the long term, with the collection of muscle and blood samples for testing.

Work at the Center for Cachexia Research Innovation and Therapy

The Center for Cachexia Research, Innovation and Therapy brings together investigators, institutions, patients, and resources on cachexia in the US. It aims to support clinical studies on cachexia diagnosis and treatment using a multi-pronged approach that involves advanced molecular genetics, pharmacological, imaging, and psychosocial analysis. The main goals of the center are:

• to build a multi-disciplinary group that shares ideas, resources, techniques, and best practices
• to promote both inter- and intra-institutional collaboration, joint investments as well as publications
• to stimulate novel discoveries in the field of cancer and other cachexias

Research work at the center focuses on understanding how cytokines or growth factors secreted by tumors affect muscle function and aging in chronically ill patients, and the role of metastatic bone disease in causing cancer cachexia.

Breakthrough at La Trobe University

In September 2015, scientists at the La Trobe University, Melbourne, discovered what causes cancer cachexia, which has already spurred work on drug development to arrest the condition. According to this ground-breaking research by a 28-member team of international researchers, the fibroblast growth factor-inducible 14 (Fn14) receptor found on the membrane of cancer cells causes this muscle-wasting condition.

Earlier, it was thought that the weight-loss and muscle wasting that is so often seen in end-stage cancer patients is due to the spread of the tumor throughout the body, causing nutritional complications and anorexia. However, this later research led by the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, blocking the Fn14 receptor can help reverse cachexia, regardless of the presence or stage of a tumor.

This study has been published in Cell, an international life sciences journal. The Co-operative Research Centre for Biomarker Translation funded the original research work, while the current work is funded by the NHMRC.

This finding is a game-changer as regards the life of end-stage cancer patients, for whom arresting cachexia translates into remarkably better functional performance and quality of life. It will also allow continuing chemotherapy in late-stage disease, which is not currently possible in most cases because of the patient’s extreme weakness, owing to progressive muscle wasting and weight loss.

According to the lead author of the paper, Dr. Amelia Johnston, the treatment approach for reversing cachexia on the basis of their discovery would be developing a specific antibody against the Fn14 receptor, which would also help arrest the condition with minimal side effects.

The team is now preparing to develop the antibody therapy for human trials in collaboration with researchers from the Olivia Newton-John Cancer Research Institute.

References

• http://www.nature.com/news/cachexia-the-last-illness-1.18961
• http://www.latrobe.edu.au/news/articles/2015/release/major-discovery-into-cancer-weight-loss3
• http://www.cancer.iu.edu/research-trials/cachexia-center.shtml
• http://journals.lww.com/co-clinicalnutrition/Abstract/2016/07000/Fn14___a_new_player_in_cancer_induced_cachexia.14.aspx