The role of CD36 in renal and bladder cancer.

CD36 functions as both a lipid transporter and scavenger receptor, integrating metabolic and inflammatory signaling pathways. It plays a critical role in maintaining cellular homeostasis and influencing disease progression. This review summarizes the structure, ligands, functions, regulation, and clinical implications of CD36 in renal and bladder cancer. Increased CD36 expression promotes enhanced fatty acid uptake, which supports tumor cell proliferation, migration and survival, by mediating metabolic reprogramming and interacting with the tumor microenvironment. In renal cancer, most frequently clear cell renal carcinoma (ccRCC), which has a typical metabolic phenotype, CD36 is involved in lipid accumulation and oxidative stress pathways. Pathogenic mechanisms include hypoxia-inducible factor (HIF)-driven pathways and carnitine palmitoyl transferase 1A (CPT1A) via the PPARα/CD36 axis, which phosphorylate Akt. By using fatty acid oxidation, CD36 lead to the production of reactive oxygen species and to transcription of genes mediating a pro-tumor function, inducing tumor-associated macrophages (TAM). In bladder cancer, CD36 is implicated in tumoral cells proliferation, survival, and adaptation to metabolic stress, epithelial-mesenchymal transition (EMT) and influences the tumor microenvironment, through interactions with tumor-associated macrophages and inflammatory signaling pathways. Although multiple studies propose CD36 as a prognostic biomarker, inconsistencies across cohorts limit its clinical translation. Notably, advances have revealed the regulatory networks governing distinct physiological properties of CD36, thereby identifying targeting CD36 as a potential strategy for cancer treatment. Inhibition of CD36-mediated lipid metabolism and signaling pathways may reduce tumor growth and metastatic potential. However, further research is necessary to clarify its context-dependent functions and to develop effective CD36-targeted therapies. To our knowledge, this is the first review to systematically examine the role of CD36 across both renal and bladder cancer. It could be the first step toward identifying new mechanisms mediated by CD36 in these malignancies.