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MINI REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1537808
This article is part of the Research Topic Integrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and Oncology View all 12 articles

Redefining Bladder Cancer Treatment: Innovations in Overcoming Drug Resistance and Immune Evasion

Provisionally accepted
Peng Huang Peng Huang 1Jie Wang Jie Wang 1Zongze Yu Zongze Yu 1*Jiaan Lu Jiaan Lu 2*Zhou Sun Zhou Sun 3*Zhigui Chen Zhigui Chen 1*
  • 1 Department of Urology, Second People's Hospital of Meishan City, Meishan, China
  • 2 Southwest Medical University, Luzhou, China
  • 3 Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Hebei Province, China

The final, formatted version of the article will be published soon.

    Bladder cancer is one of the most common malignancies of the urinary system and has always presented great challenges in treatment due to its intricate biological features and high recurrence rates. Although great developments were achieved in immunotherapy and targeted therapies within the last decade, therapeutic outcomes for a great number of patients remain unsatisfactory, particularly as to long-term efficacy. Review discusses the molecular mechanisms developed during the process of bladder cancer progression: genetic and epigenetic alterations, dynamics of the tumor microenvironment (TME), and dysregulation and abnormal activation of various signaling pathways -all contributing to therapeutic resistance. It is genetic mutation, especially in both low-and high-grade tumors, that, alongside epigenetic modifications, plays a considerable role in tumor aggressiveness and drug resistance. TME, comprising cancer-associated fibroblasts (CAFs), immunosuppressive cells, and different components of the extracellular matrix (ECM), orchestrates a setting that fosters tumor growth and immune evasion and confers resistance on any therapeutic regime that might be used. The review also provides an overview of PI3K/AKT and MAPK signaling pathways in the progression of bladder cancer and the development of targeted therapies against them.Further, it discusses the challenges and mechanisms of resistance to immunotherapy, including those involving immune checkpoint inhibitors. Other promising approaches include the development of new therapeutic strategies that target not only the signaling pathways but also immune checkpoints in combination therapies. This review aims to contribute to the elaboration of more effective and personalized treatment strategies by fully understanding the underlying mechanisms involved in bladder cancer.

    Keywords: Bladder cancer, Drug Resistance, Tumor Microenvironment, precision therapy, combined therapy

    Received: 01 Dec 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Huang, Wang, Yu, Lu, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zongze Yu, Department of Urology, Second People's Hospital of Meishan City, Meishan, China
    Jiaan Lu, Southwest Medical University, Luzhou, China
    Zhou Sun, Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, 130033, Hebei Province, China
    Zhigui Chen, Department of Urology, Second People's Hospital of Meishan City, Meishan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.