Unveiling the TGF-β/Smad signaling in renal carcinoma progression: Prognostic and therapeutic insights

About 2 to 3 % of all new cancer cases worldwide are renal carcinomas. Nevertheless, during the past few decades, there has been a 2 % annual increase in the prevalence of this malignancy worldwide. Within three years, 20 to 40 % of individuals with early-stage malignancies may either have a local recurrence or metastasis, and 20 to 30 % will receive a diagnosis of metastatic illness. For renal cancer, traditional chemotherapy and radiation are ineffective, while metastatic-focused treatments are linked to several side effects and the quick emergence of resistance. As a silent disease with no specific and identifiable signs and symptoms and an aggressive nature, there is an urgent need to discover trustworthy prognostic biomarkers as well as novel therapeutic targets. With multiple studies suggesting that renal carcinoma is a disease with complex genomic and epigenomic backgrounds influencing tumor development and progression, it is essential to study the dysregulated cellular pathways behind this disease to address this need. In this context, the canonical TGF-β signaling pathway could reveal interesting clues. The current study attempts to outline the role of this signaling mechanism in renal cancer dynamics, with a focus on its potential prognostic, predictive, and therapeutic relevance.