Emerging roles of autophagy in the development and treatment of urothelial carcinoma of the bladder

ABSTRACT

Introduction

High recurrence rates, frequent surveillance strategies, and current multidisciplinary treatment approaches make urothelial carcinoma of bladder (UCB) one of the most expensive cancers to clinically manage. Recent studies have demonstrated a role for autophagy in bladder tumorigenesis. It serves as a tumor suppressor by maintaining genomic integrity and preventing tumor proliferation during initial stages of tumor development. Nevertheless, once established, cancer cells may utilize protective autophagy to endure cellular stress and survive in the adverse environment. Its excessive stimulation supports cancer cells' resistance to therapeutic modalities.

Areas Covered

PubMed and Google Scholar electronic databases were searched for recently published studies. This review summarizes emerging roles of autophagy in development/progression of UCB and treatment resistance and explores novel therapeutic targets for prevention of cancer invasion, metastatic spread', and disease relapse.

Expert Opinion

The development of novel therapies via targeting of autophagy may augment current treatment regimens and improve clinical outcomes. Synthetic compounds or plant-based metabolites are reported to enhance cancer therapies by modulating autophagic flux. Successful autophagy-focused therapeutic intervention requires a mechanistic understanding of autophagic effects on tumor initiation and progression and the development of efficient biomarkers to monitor it in tumor tissues.

KEYWORDS:

• Apoptosis
• Autophagy
• Cell survival
• Therapeutic resistance
• Urothelial carcinoma of bladder

Article Highlights

• High recurrence rates, frequent surveillance strategies, and current multidisciplinary treatment approaches make urothelial carcinoma of bladder (UCB) one of the most expensive cancers to clinically manage.

• Autophagy maintains the nutrient and energy homeostasis, but its dysregulation results in the cellular traffic jam and contributes to the development of clinically different subsets of bladder cancer.

• Development of novel therapies based on the application of autophagic modulators improves clinical outcomes by sensitizing cancer cells toward already existing chemotherapy, radiotherapy, and/or immunotherapy.

• Preclinical studies and clinical trials are necessary to assess and validate the efficacy of the regulators of autophagic flux with reduced toxicity for their inclusion as a primary or an adjunct option in the treatment of bladder cancer.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Additional information

Funding

This work was supported by the Indian Council for Medical research, Government of India (grant no. 5/3/8/24/2020-ITR).