Cancer Grand Challenges is series of £20m ($25m) awards that give international teams of researchers the freedom to think differently, act creatively and explore truly innovative science to take on fundamental questions in cancer.
Many patients with advanced cancer suffer from a devastating syndrome termed cachexia. This is characterised by significant weight loss from both loss of skeletal muscle and fatty tissue that can’t be reversed by nutritional support. These symptoms are often accompanied by fatigue and a declining performance status that imparts a poor prognosis. Understanding the causal mechanism of this syndrome would open the door for the development of novel interventions, which could improve treatment response, quality of life, and survival.
Barriers and opportunities
Cachexia, fatigue, and poor performance status are common problems in patients with advanced cancer. Although there is a limited understanding of the molecular basis of these clinical phenomena, current research has suggested that these may be a result of a complex set of interactions between the tumour and the patient that includes release of inflammatory cytokines and tumour and host metabolic changes. Research has begun to uncover some cancer cell intrinsic mechanisms, but we know little about how tumours interact with the stroma and host in this setting. Pre-clinical and clinical studies have generated plausible mediators of cachexia, however, there has been little impact on patient benefit when such mediators are targeted in clinic.
This calls for bold new approaches to better understand and treat cachexia, fatigue and declining performance status. This might include:
- Generating a deeper molecular understanding of cachexia and fatigue
- Can preclinical models be developed that recapitulate these conditions?
- Can we identify methods to manipulate the pathways involved and identify treatment targets?
- Are there biomarkers predicting the onset of cancer cachexia? And once identified could these lead to the development of biomarker driven clinical trials to prevent or reverse its onset?
Vision and Impact
This challenge seeks to expand our mechanistic understanding of cachexia, fatigue, and poor performance status that severely impact the quality of life of cancer patients and limit our ability to deliver systemic therapies. Please note, although we recognise that many patients may have prolonged treatment-related fatigue, the focus of this challenge should be on addressing and reversing the causal mechanisms of cancer cachexia, declining performance status and fatigue independent of therapy.
It will require a multidisciplinary research team that could include expertise in metabolism, endocrinology, biology, immunology, neurohormonal biology, clinical oncology, chemistry and pharmacology.