Urologic oncology has seen significant advances in precision therapy, with immunotherapy and organoid-based approaches at the forefront. Immunotherapy offers transformative potential for improving patient outcomes, driving research into novel agents and combination regimens. Concurrently, organoids can recapitulate the characteristics of the original tumors, allowing for personalized drug testing and the prediction of treatment responses. They have opened new avenues for personalized medicine, enabling more accurate drug screening and treatment planning. Using immune co-culture technology, breakthroughs have been achieved in the immunotherapy of tumors. Despite these exciting advancements, many aspects of immunotherapy and organoid-based precision medicine in urologic tumors remain unclear. The complex interplay between the immune system and tumors, as well as the challenges in translating organoid-based research into clinical practice, warrants further exploration.

This Research Topic aims to address critical barriers in urologic tumor precision therapy: (1) suboptimal efficacy and immune resistance in immunotherapy, (2) limited biomarkers for predicting response, and (3) challenges in standardizing and clinically translating organoid models.

Recent advances provide pathways forward:
• New Immunotherapies: Novel immunotherapeutic drugs and combination regimens targeting multiple immune checkpoints or combining with other therapies are being developed. These show potential in enhancing efficacy and reducing side effects.

• Immune sensitivity/resistance: The tumor microenvironment has emerged as a key regulator. Strategies to block immunosuppressive molecules or leverage new biomarkers (e.g., cytokine profiles) are being developed to overcome resistance and boost sensitivity.

• Organoid refinement: Improved techniques enable better tumor recapitulation. Co-culturing organoids with immune cells helps simulate the in vivo environment, thereby facilitating the development of more effective immunotherapies.

• Genetic-driven precision therapy: Advances in genetic profiling have accelerated targeted treatment development. PARP inhibitors have demonstrated remarkable efficacy in urologic tumors harboring HRR (Homologous Recombination Repair) gene mutations, offering a novel therapeutic option for patients with limited conventional treatment responses. Meanwhile, belzutifan has emerged as a breakthrough agent for VHL (von Hippel-Lindau) disease-associated tumors and pheochromocytoma, targeting the underlying genetic aberrations to inhibit tumor growth and progression. These gene-based strategies highlight the potential of molecular subtyping in guiding personalized treatment decisions.

We welcome submissions of the following article types: Brief Research Report, Correction, Editorial, General Commentary, Hypothesis & Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Policy and Practice Reviews, Review, Systematic Review, Technology and Code.

Submission topics include:
• Develop and evaluate new immunotherapeutic drugs and regimens for urologic tumors using genomics

• Study the genetic and molecular determinants of immune sensitivity in urologic tumors, focusing on how genomic variants and gene-expression programs in tumor-associated immune cells and cytokine networks influence responsiveness.

• In-depth research on immune resistance in urologic tumors, including the identification of resistance-related genes and pathways, and potential strategies to overcome resistance.

• Apply organoid-based precision oncology to urologic tumors by integrating genomic and transcriptomic profiling to establish models, screen potential drugs and immunotherapies, and generate actionable diagnostic and prognostic insights.

• Genetic mechanism research of urologic tumors, focusing on HRR gene mutations, VHL gene abnormalities, and other key genetic alterations related to tumorigenesis and progression.

• Clinical and preclinical studies on targeted therapies for genetically driven urologic tumors, such as PARP inhibitors and belzutifan.

• Development and validation of genetic biomarkers for predicting treatment response and prognosis in urologic tumors.

This Topic seeks contributions that leverage these advances to deepen mechanistic understanding, identify robust biomarkers, standardize organoid methodologies, and translate findings into clinical practice—ultimately enhancing the precision, efficacy, and durability of treatment for urologic cancers.

Authors

Frontiers in Genetics

Cancer Genetics and Oncogenomics