Cancer cachexia (CC) is a multifactorial syndrome characterized by progressive weight loss, anorexia, and loss of skeletal muscle and fat mass, resulting in reduced quality of life and poor prognosis. Currently, there are no approved pharmacological treatments for CC, highlighting the urgent need for developing novel experimental models.

This review covers recent advancements in preclinical models of CC, highlighting their implications for drug discovery and therapeutic development. The literature search was conducted in PubMed up to April 2025.

CC remains clinically challenging and requires improved translational research and therapeutic strategies. Improved preclinical models, such as personalized patient-derived xenograft models incorporating patient-specific immune profiles and microbiota, hold promise for precision medicine.

Identification of standardized extracellular vesicle (EV) derived biomarkers and effective targeting of EV signaling pathways are critical research directions. In addition, clinical validation of appetite regulators such as glucagon-like peptide-1 and growth differentiation factor-15, along with comprehensive approaches integrating diet, exercise, and targeted pharmacological interventions, will be pivotal.

Finally, multidisciplinary collaboration is essential to translate these findings into meaningful therapies that will ultimately improve patient prognosis and quality of life.