Curated Papers > In recent years, high-impact research on "single-cell sequencing" (IF≥30, past 5 years)

Treatment of muscle-invasive and advanced bladder cancer in 2020.

Literature Information

DOI	10.3322/caac.21631
PMID	32767764
Journal	CA: a cancer journal for clinicians
Impact Factor	232.4
JCR Quartile	Q1
Publication Year	2020
Times Cited	558
Keywords	antibody-drug conjugates, bladder cancer, fibroblast growth factor receptor (FGFR), genitourinary, immunotherapy
Literature Type	Journal Article, Review
ISSN	0007-9235
Pages	404-423
Issue	70(5)
Authors	Vaibhav G Patel, William K Oh, Matthew D Galsky

TL;DR

Bladder cancer, responsible for approximately 170,000 deaths annually, has historically been treated with platinum-based chemotherapy; however, recent advancements in genomic characterization have unveiled therapeutic vulnerabilities and led to the approval of immune checkpoint inhibitors and targeted therapies. This evolving landscape not only enhances our understanding of bladder cancer's molecular characteristics but also paves the way for improved treatment strategies for both advanced and muscle-invasive forms of the disease.

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antibody-drug conjugates · bladder cancer · fibroblast growth factor receptor (FGFR) · genitourinary · immunotherapy

Abstract

Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.

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Primary Questions Addressed

1. What are the key differences in treatment approaches for muscle-invasive versus advanced bladder cancer?
2. How have recent advancements in genomic characterization influenced the development of targeted therapies for bladder cancer?
3. What role do immune checkpoint inhibitors play in the management of advanced bladder cancer, and how do their efficacy rates compare to traditional chemotherapy?
4. In what ways can the findings from the molecular characterization of bladder cancer inform future treatment strategies?
5. What are the implications of high mutational burden in bladder cancer for patient selection in clinical trials for new therapies?

Key Findings

Key Insights

1. Research Background and Purpose: Bladder cancer is a significant global health concern, responsible for approximately 170,000 deaths annually. Historically, the treatment of muscle-invasive and advanced bladder cancer has relied heavily on platinum-based chemotherapy for over 40 years. The purpose of the study is to review the recent advancements in understanding bladder cancer pathogenesis through genomic characterization and to explore the evolving therapeutic landscape, including the introduction of immune checkpoint inhibitors and targeted therapies. The authors aim to highlight these developments and their implications for treatment strategies.

2. Major Methods and Findings: The study synthesizes findings from the last decade, particularly advancements in sequencing technologies that have improved the genomic characterization of bladder cancer. This progress has revealed a high mutational burden in bladder cancer, prompting the investigation of immune checkpoint inhibitors, which have shown durable responses in some patients with advanced disease. Furthermore, the authors discuss the emergence of targeted therapies, including fibroblast growth factor receptor (FGFR) inhibitors and antibody-drug conjugates, which utilize commonly expressed molecular targets. The review also addresses how these molecular insights are shaping treatment approaches for muscle-invasive bladder cancer.

3. Core Conclusions: The study concludes that the treatment landscape for muscle-invasive and advanced bladder cancer is undergoing a significant transformation. The integration of genomic profiling has not only enhanced the understanding of the disease but has also facilitated the development of innovative therapies that go beyond traditional chemotherapy. Immune checkpoint inhibitors and targeted therapies are now integral components of treatment regimens, providing new avenues for improving patient outcomes.

4. Research Significance and Impact: This research is significant as it underscores a paradigm shift in the management of bladder cancer, highlighting the importance of personalized medicine. The identification of molecular characteristics and therapeutic vulnerabilities paves the way for tailored treatment strategies that could enhance efficacy and minimize toxicity. Additionally, the findings encourage ongoing investigations into optimizing treatment regimens, potentially leading to improved survival rates and quality of life for patients with muscle-invasive and advanced bladder cancer. The insights presented in this study are crucial for clinicians and researchers as they navigate the evolving landscape of bladder cancer treatment and strive to implement cutting-edge therapies into clinical practice.

Literatures Citing This Work

1. [Molecular subtypes of urothelial carcinoma of the bladder-background and clinical relevance]. - Philipp Erben;Christoph Becker;Igor Tsaur;Matthias B Stope;Tilman Todenhöfer; - Der Urologe. Ausg. A (2021)
2. A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures. - Marika Mokou;Vasiliki Lygirou;Ioanna Angelioudaki;Nikolaos Paschalidis;Rafael Stroggilos;Maria Frantzi;Agnieszka Latosinska;Aristotelis Bamias;Michèle J Hoffmann;Harald Mischak;Antonia Vlahou - Cancers (2020)
3. Clinical Perspectives of ERCC1 in Bladder Cancer. - Konstantinos Koutsoukos;Angeliki Andrikopoulou;Nikos Dedes;Flora Zagouri;Aristotelis Bamias;Meletios-Athanasios Dimopoulos - International journal of molecular sciences (2020)
4. Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis. - Weiting Kang;Qiang Wang;Yun Dai;Hanbo Wang;Muwen Wang;Jin Wang;Dong Zhang;Peng Sun;Taiguo Qi;Xunbo Jin;Zilian Cui - Cell death & disease (2020)
5. Present Status, Limitations and Future Directions of Treatment Strategies Using Fucoidan-Based Therapies in Bladder Cancer. - Yasuyoshi Miyata;Tomohiro Matsuo;Kojiro Ohba;Kensuke Mitsunari;Yuta Mukae;Asato Otsubo;Junki Harada;Tsuyoshi Matsuda;Tsubasa Kondo;Hideki Sakai - Cancers (2020)
6. Novel Tyrosine Kinase Targets in Urothelial Carcinoma. - Javier Torres-Jiménez;Víctor Albarrán-Fernández;Javier Pozas;María San Román-Gil;Jorge Esteban-Villarrubia;Alfredo Carrato;Adriana Rosero;Enrique Grande;Teresa Alonso-Gordoa;Javier Molina-Cerrillo - International journal of molecular sciences (2021)
7. CircRNAs: Emerging Bladder Cancer Biomarkers and Targets. - Zhaofeng Liang;Wenhao Guo;Shikun Fang;Yue Zhang;Ling Lu;Wenrong Xu;Hui Qian - Frontiers in oncology (2020)
8. Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy. - Shupeng Wang;Shaohua Jin;Qinghai Shu;Song Wu - Pharmaceutics (2021)
9. circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling. - Jiang Zhu;Yuming Luo;Yue Zhao;Yao Kong;Hanhao Zheng;Yuting Li;Bowen Gao;Le Ai;Hao Huang;Jian Huang;Zhihua Li;Changhao Chen - Molecular therapy : the journal of the American Society of Gene Therapy (2021)
10. Exploration of a Robust and Prognostic Immune Related Gene Signature for Cervical Squamous Cell Carcinoma. - Zhihua Zuo;Junjun Xiong;Chuyi Zeng;Yao Jiang;Kang Xiong;Hualin Tao;Yongcan Guo - Frontiers in molecular biosciences (2021)

... (548 more literatures)

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