The intricate role of adipokines in cancer-related signaling and the tumor microenvironment: Insights for future research

Obesity represents a global health challenge, with adipose tissue acting as a highly active endocrine organ that synthesizes and secretes a diverse array of bioactive proteins, known as adipokines. These cell signaling molecules regulate metabolic equilibrium, inflammatory cascades, and immune surveillance, exerting substantial systemic effects. A growing body of evidence has also highlighted their key role in cancer biology, through their intricate impact on oncogenic signaling networks and the tumor microenvironment (TME). The TME, a highly dynamic and heterotypic network composed of malignant cells, infiltrating immune cells, stromal constituents, and extracellular matrix elements, facilitates tumor evolution and immune evasion. Among adipokines, adiponectin and leptin have been extensively studied. Research has shown that adiponectin exhibits tumor-suppressive properties, whereas leptin enhances proliferative, angiogenic, and inflammatory pathways that promote malignancy. However, these effects are context-dependent and, at times, contradictory across different studies. Furthermore, the functional landscape of adipokines in cancer extends beyond these paradigms, with emerging research identifying a broader spectrum of novel adipokines involved in cancer reprogramming. This review delineates the molecular interplay between adipokines and oncogenic pathways, elucidating their mechanistic contributions to TME crosstalk and immune modulation. Additionally, we examine their potential as diagnostic and prognostic biomarkers and assess their viability as therapeutic targets for precision oncology. By integrating current evidence and identifying unresolved questions, this review aims to refine our understanding of adipokine-driven tumor biology and establish a platform for future research.