Open Access

REVIEW

Mitochondrial Dysfunction in Renal Cell Carcinoma: A Comprehensive Review of Pathogenic Mechanisms and Emerging Therapeutic Opportunities

Yanhong Wang^1,#, Junbo Liu^2,#, Qiaoping Xu^3,#, Zhao Ma^4,*

1 Department of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2 Department of Pharmacy, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
3 Department of Pharmacy, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China
4 Department of Pharmacy, Hangzhou Third People’s Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China

* Corresponding Author: Zhao Ma. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Advances in Genitourinary Cancer)

Oncology Research 2026, 34(9), 14 https://doi.org/10.32604/or.2026.082432

Received 16 March 2026; Accepted 20 July 2026; Issue published 13 August 2026

Abstract

In renal cell carcinoma (RCC), alterations in cellular metabolism are a defining feature, among which impaired mitochondrial function stands out as a key factor influencing both tumor aggressiveness and patient responses to therapy. The aim of this review is to systematically synthesize current knowledge on the role of mitochondrial dysfunction in RCC pathogenesis and to explore emerging therapeutic strategies targeting mitochondrial vulnerabilities. This comprehensive analysis examines the integrated dysregulation of core mitochondrial processes—bioenergetic metabolism, organelle dynamics, programmed cell death pathways, redox homeostasis, and selective autophagy—in driving RCC pathogenesis. Our synthesis reveals how genetic drivers, molecular regulators, and microenvironmental cues converge to remodel mitochondrial function, creating both adaptive advantages and therapeutic vulnerabilities. A paradoxical duality emerges in mitochondrial biology: processes such as fission, mitophagy, and reactive oxygen species (ROS) generation can simultaneously support tumor adaptation while rendering cells susceptible to targeted interventions. We evaluate emerging therapeutic approaches directed at mitochondrial vulnerabilities, including metabolic inhibitors, nanoscale delivery systems, and phytochemical agents, while addressing current limitations in specificity and resistance mechanisms. Based on current preclinical evidence, this integrated perspective establishes mitochondrial dysfunction as a central determinant of RCC malignancy and suggests potential combinatorial strategies for precision oncology approaches that warrant further investigation.

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Keywords

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