The host matters: Integrating resting energy expenditure into personalized medicine beyond tumor-centered approaches.

BACKGROUND AND AIMS: Malnutrition is one of the most frequent and significant complications of cancer, driven by cachexia, a multifactorial metabolic syndrome characterized by systemic inflammation, anorexia, and progressive loss of muscle mass and function. It affects up to 80% of patients with cancer and contributes to treatment intolerance, reduced quality of life, and poor survival. Despite its major nutritional and prognostic burden, cachexia-related malnutrition remains insufficiently characterized and inadequately managed in routine oncology practice.

METHODS

We conducted a narrative review of the current literature on the pathophysiology of cancer cachexia, the role of resting energy expenditure (REE) as an emerging host depending metabolic biomarker, nutritional recommendations, and therapeutic strategies targeting cachexia, such as adapted physical activity and anti-cachexia pharmacological agents.

RESULTS

Cancer cachexia results from tumor-host metabolic interactions involving pro-inflammatory cytokines, skeletal muscle proteolysis, adipose tissue browning, and tumor-derived endocrine mediators such as GDF-15. REE measurement by indirect calorimetry identifies hypermetabolism as an independent prognostic factor across cancer types and treatments, including immunotherapy. Current nutritional recommendations lack granularity and do not account for individual metabolic phenotypes, cancer type, disease stage, or therapeutic modality. Emerging therapies, including GDF-15 inhibitors, offer promising but still incomplete responses to cachexia-related wasting.

CONCLUSION

Addressing cancer cachexia requires extension of tumor-centered precision oncology to the management of the tumor-bearing host. A personalized medicine approach integrating REE, given its growing evidence for prognostic and clinical utility, with nutritional support, adapted physical activity, and targeted anti-cachexia therapies, all coordinated by the oncologist, represents a promising path forward.