Cancer Cachexia Research and Drug Development: Lessons from Failures and the Promise of Immunomodulation
TL;DR
This review summarizes the progression of cachexia research, highlighting key findings involving inflammatory cytokines, proteolytic pathways, mitochondrial dysfunction, and immune dysregulation, and novel immunomodulatory strategies, including R-ketorolac, which may restore immune homeostasis and target the root causes of cachexia.
Abstract
Simple Summary Cancer cachexia is a serious condition that affects individuals with cancer, causing an ongoing loss of muscle and occasionally body fat, resulting in weakness, fatigue, reduced quality of life, and poor response to treatment. Unlike ordinary weight loss, cancer cachexia cannot be reversed by eating more or improving nutrition. It is driven by complex interactions among the tumor, the immune system, inflammation, and changes in the body’s metabolism. This review describes the evolution of cancer cachexia and why many treatments targeting a single biological pathway have failed to improve patient outcomes. Current evidence suggests that more effective management will require a combination of approaches, such as medicines, nutritional support, exercise and rehabilitation, tailored to the patient’s condition. Emerging treatments, such as immunomodulatory therapies, restore immune balance and may address the underlying causes of cachexia and offer new therapies for improving treatment tolerance, physical function and survival in patients with cancer.