Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults and is recognized as one of the most lethal cancers, largely due to the absence of early symptoms and frequent late-stage diagnosis. Among RCCs, localized RCC offers a relatively promising prognosis, but the survival rate declines sharply in metastatic cases. Research on genetic, lifestyle, and hereditary risk factors-including obesity, smoking, von Hippel-Lindau syndrome, and Tuberous Sclerosis-alongside advancements in genetic screening, proteomics, and immunohistochemistry, has led to the identification of novel biomarkers and therapeutic targets. Despite these advances, more refined methods for early detection and comprehensive treatment strategies remain critically needed.

Clear cell RCC (ccRCC), the predominant and most aggressive subtype, is characterized by VHL gene inactivation and resulting dysregulation of hypoxia pathways. While ccRCC accounts for approximately 80% of RCC cases, other forms often lack identifiable hereditary mutations, highlighting the disease’s complex molecular heterogeneity. This complexity, combined with metabolic reprogramming and the influence of tumor microenvironment (TME), contributes to tumorigenesis and therapy resistance. Innovative research highlights metabolic reprogramming like the Warburg effect, disruptions in cellular processes, and the immune-suppressive role of the TME as key factors in disease progression. Current treatment strategies combine tyrosine kinase inhibitors (TKIs), angiogenesis blockers, and immune checkpoint inhibitors; nevertheless, drug resistance remains a substantial barrier to long-term success. Emerging therapies, including cancer vaccines and CAR-T cell therapy, offer promising prospects for cases refractory to standard treatments. However, advancements in early detection, personalized medicine, and immunotherapy are essential for improving long-term outcomes for RCC patients globally.

This Research Topic aims to explore pathogenesis of RCC and state-of-the-art therapeutic strategies. Our goal is to refine diagnostic technologies, identify novel molecular targets, and enhance combination therapies to improve survival outcomes in RCC patients. We encourage contributions that pioneer advancements in early detection, personalized medical approaches, and immunotherapy applications— pivotal elements in transforming patient prognosis worldwide.

To gather further insights into RCC research, we welcome articles addressing, but not limited to, the following themes:
o Investigations of immune signatures and biomarkers associated with RCC
o Multi-omics approaches to identify predictive biomarkers of treatment response in RCC
o The role of metabolite dysfunction, such as mitochondrial dysfunction and lipid metabolism, in RCC progression
o Mechanisms underlying resistance to TKIs and immune checkpoint inhibitors (ICIs), and strategies for overcoming therapy resistance in advanced RCC
o Strategies for reprogramming the TME by targeting cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) that promote immunosuppression
o Emerging immunotherapies and novel cell therapies, including the development of neoantigen vaccines and CAR-T/NK cell therapy targeting RCC-specific antigens
o Advances in precision medicine for RCC, such as single-cell sequencing to decipher intratumoral heterogeneity and clonal evolution
o Applications of artificial intelligence (AI), including AI-driven radiopathomics for early diagnosis and prediction of treatment response, and machine learning models for multi-omics data integration

Are you interested in contributing a manuscript to this Research Topic?

Unraveling Renal Cell Carcinoma: Pathogenesis, Therapeutic Strategies, and Future Perspectives