BCG therapy in bladder cancer and its tumor microenvironment interactions

Area of Science:

• Oncology
• Immunotherapy
• Microbiology

Background:

• Bacillus Calmette-Guérin (BCG) has been the gold standard for non-muscle-invasive bladder cancer (NMIBC) treatment for over 30 years.
• Despite its efficacy, challenges include unclear mechanisms, 30-50% resistance rates, and significant side effects.
• Understanding BCG's interaction with the tumor microenvironment and bladder microbiome is crucial.

Purpose of the Study:

• To provide an updated discussion of BCG's antitumor mechanisms in bladder cancer.
• To analyze current research on BCG resistance and explore strategies to improve BCG-based immunotherapy.
• To offer insights for developing novel bacterial therapies in oncology.

Main Methods:

• Review of preclinical and clinical studies on BCG's antitumor mechanisms and resistance.
• Analysis of BCG's interactions with bladder cancer cells and the tumor microenvironment.
• Incorporation of recent research on BCG and the bladder microbiome.

Main Results:

• BCG exerts antitumor effects through direct actions and interactions within the tumor microenvironment.
• Both intrinsic and adaptive resistance mechanisms to BCG in bladder cancer have been identified.
• Emerging strategies include recombinant BCG, combination therapies, optimized regimens, and microbiome targeting.

Conclusions:

• Improving BCG immunotherapy requires addressing resistance, reducing toxicity, and enhancing efficacy.
• Targeting the bladder microbiome presents a novel therapeutic avenue.
• Lessons from BCG inform the development of future bacterial therapies for cancer treatment.