Modeling cancer cachexia: from preclinical platforms to biosensing innovations.

Cancer cachexia is a multifactorial and progressive syndrome characterized by the not fully reversible loss of skeletal muscle and adipose tissue, which significantly impairs treatment tolerance, quality of life, and patient survival. Despite its high clinical burden, cachexia remains underdiagnosed and undertreated, largely because current diagnostic criteria rely on late-stage clinical manifestations, such as weight loss, and reliable biomarkers for early detection are still lacking. In addition, available therapeutic strategies are mostly palliative and fail to target the underlying mechanisms of the syndrome. A deeper understanding of the molecular and systemic drivers of cachexia is therefore essential for the development of effective interventions. In this context, preclinical models have become indispensable tools for investigating disease mechanisms, identifying therapeutic targets, and validating biomarkers under controlled conditions. Herein, we review the main preclinical platforms used to study cancer cachexia, including in vivo, in vitro, and emerging microphysiological systems, highlighting their respective strengths and limitations in recapitulating tumor-host interactions and tissue wasting. Further, we highlight the need for advanced biosensing technologies as promising tools for the sensitive detection of predictive cachectic biomarkers, with potential applications in early detection, disease monitoring, and translational research. Together, these approaches may accelerate the future development of mechanism-based strategies for cancer cachexia.