---
title: "Targeted and Immune Therapies for Renal Cell Carcinoma: Molecular Drivers and Clinical Trial Evide"
id: "pubmed-42885310"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42885310"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42885310/"
doi: "10.3892/mmr.2026.14041"
published_at: "2026-10-16T12:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Targeted and Immune Therapies for Renal Cell Carcinoma: Molecular Drivers and Clinical Trial Evide
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42885310
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42885310/)
- **DOI:** [10.3892/mmr.2026.14041](https://doi.org/10.3892%2Fmmr.2026.14041)
- **Published At:** 2026-10-16T12:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The review synthesized molecular and clinical evidence on **renal cell carcinoma** (RCC), emphasizing dysregulated angiogenesis, immune evasion and epigenetic/chromatin remodeling as core disease drivers. - Investigators summarized pathway biology centered on von Hippel‑Lindau (VHL)–hypoxia‑inducible factor (HIF) signaling and downstream **VEGF**-mediated angiogenesis, linking biology to therapeutic targets. - The article reviewed phase III trial data for **VEGF-targeted tyrosine kinase inhibitors**, mechanistic target of rapamycin inhibitors and **immune checkpoint inhibitors**, and considered combination regimens such as **nivolumab plus ipilimumab**, **pembrolizumab + axitinib** and **lenvatinib + pembrolizumab**. - Emerging biomarkers were cataloged: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups, programmed death‑ligand 1 (PD‑L1) expression, and chromatin remodeling gene alterations (polybromo 1/BRG1‑associated factor 180, BRCA1‑associated protein 1, and SET domain containing 2). - The review noted that durable, predictive biomarkers and optimal sequencing strategies remain unresolved; therapy resistance arises through adaptive angiogenic signaling, immune escape and metabolic reprogramming. - Authors proposed integrated multi‑omics and rational combinations as paths forward but indicated the need for further clinical validation and clearer clinical utility of proposed biomarkers. - Methodology: this is a narrative review integrating molecular biology with clinical trial literature; specific trial design parameters, patient numbers and statistical values were not reported in the abstract and are not available in the source summary.
## Clinical Analysis & Structured Key Points
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Epub 2026 Oct 16. # Navigating the landscape of targeted therapies for renal cell carcinoma in the era of precision medicine (Review) [Hongguo Cui](https://pubmed.ncbi.nlm.nih.gov/?term=Cui+H&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Jingheng Song](https://pubmed.ncbi.nlm.nih.gov/?term=Song+J&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Peisen Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+P&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Zhengchao Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Z&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yuanyuan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Gang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+G&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Aimin Tian](https://pubmed.ncbi.nlm.nih.gov/?term=Tian+A&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Jizhong Che](https://pubmed.ncbi.nlm.nih.gov/?term=Che+J&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yangyang Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Hui Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+H&cauthor_id=42885310)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-2 "Research and Translational Center for Immunological Disorders, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yankai Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#full-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China.") Affiliations Expand ### Affiliations * 1 Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China. * 2 Research and Translational Center for Immunological Disorders, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China. * PMID: **42885310** * DOI: [ 10.3892/mmr.2026.14041 ](https://doi.org/10.3892/mmr.2026.14041) Item in Clipboard Review # Navigating the landscape of targeted therapies for renal cell carcinoma in the era of precision medicine (Review) Hongguo Cui et al. Mol Med Rep. 2026 Dec. Show details Display options Display options Format Abstract PubMed PMID Mol Med Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mol+Med+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Mol+Med+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42885310/) . 2026 Dec;34(6):330. doi: 10.3892/mmr.2026.14041. Epub 2026 Oct 16. ### Authors [Hongguo Cui](https://pubmed.ncbi.nlm.nih.gov/?term=Cui+H&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Jingheng Song](https://pubmed.ncbi.nlm.nih.gov/?term=Song+J&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Peisen Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+P&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Zhengchao Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Z&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yuanyuan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Gang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+G&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Aimin Tian](https://pubmed.ncbi.nlm.nih.gov/?term=Tian+A&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Jizhong Che](https://pubmed.ncbi.nlm.nih.gov/?term=Che+J&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yangyang Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Hui Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+H&cauthor_id=42885310)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-2 "Research and Translational Center for Immunological Disorders, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China."), [Yankai Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42885310)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42885310/#short-view-affiliation-1 "Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China.") ### Affiliations * 1 Department of Urology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, The Second Clinical Medical School of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China. * 2 Research and Translational Center for Immunological Disorders, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, Yantai, Shandong 264100, P.R. China. * PMID: **42885310** * DOI: [ 10.3892/mmr.2026.14041 ](https://doi.org/10.3892/mmr.2026.14041) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by dysregulation of angiogenic signaling, immune evasion and epigenetic remodeling. Advances in molecular profiling have redefined RCC as a pathway‑driven disease, enabling the development of targeted therapies and immune checkpoint inhibitors (ICIs) that have notably improved clinical outcomes. The present review evaluated current evidence on the molecular basis and therapeutic landscape of RCC, with emphasis on von Hippel‑Lindau‑hypoxia‑inducible factor signaling, chromatin remodeling alterations and immune regulatory pathways. The present review summarizes pivotal phase III clinical trials evaluating VEGF‑targeted tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors, immune checkpoint inhibitors and combination regimens, including nivolumab plus ipilimumab, pembrolizumab + axitinib and lenvatinib + pembrolizumab. Emerging biomarkers, including International Metastatic Renal Cell Carcinoma Database Consortium risk stratification, programmed death‑ligand 1 expression and chromatin remodeling gene alterations (polybromo 1/BRG1‑associated factor 180, BRCA1‑associated protein 1 and SET domain containing 2), are discussed in the context of their clinical utility and limitations. Despite marked progress, durable predictive biomarkers and optimal treatment sequencing strategies remain unresolved. Resistance to therapy emerges through adaptive angiogenic signaling, immune escape and metabolic reprogramming, underscoring the need for integrated multi‑omics approaches and rational combination strategies. By integrating molecular biology with clinical trial evidence, the present review provides a structured framework for understanding therapeutic decision‑making in RCC and highlights future directions toward biomarker‑guided precision oncology. **Keywords:** biomarkers; clinical trials; immune checkpoint inhibitors; molecular mechanisms; precision medicine; renal cell carcinoma; targeted therapies; tyrosine kinase inhibitors. 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