Targeted therapies in bladder cancer: signaling pathways, applications, and challenges
Mei Peng1,2, Xuetong Chu2, Yan Peng2
1Department of Pharmacy Xiangya Hospital Central South University Changsha Hunan China.
Abstract:
Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.
Insights
Advanced bladder cancer (BC) treatments like ICIs, ADCs, and TKIs show promise, but resistance remains a challenge. Future therapies will focus on molecular pathways, metabolic reprogramming, and cancer stem cells (CSCs) to improve patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Bladder cancer (BC) is a common malignancy, particularly in men.
- Recent advances in targeted therapies have improved outcomes for advanced BC.
- Significant patient populations still experience treatment progression.
Purpose of the Study:
- To review current targeted therapies for advanced bladder cancer.
- To elucidate mechanisms of resistance and low response rates to existing treatments.
- To highlight future directions in bladder cancer drug development.
Main Methods:
- Review of current literature on targeted therapies for bladder cancer.
- Analysis of signaling pathways involved in BC progression and treatment response.
- Discussion of resistance mechanisms and potential therapeutic strategies.
Main Results:
- Immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) have shown efficacy.
- Mechanisms of low response, immune escape, toxicity, and resistance to these therapies are identified.
- Targeting metabolic reprogramming and cancer stem cells (CSCs) presents a promising future avenue.
Conclusions:
- Understanding molecular characteristics is key to improving BC survival.
- Addressing resistance and toxicity of current therapies is crucial.
- Future drug development should focus on novel targets like metabolic pathways and CSCs, guided by biomarkers and precise patient selection.
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