Current status and future prospects of antibody-drug conjugates in urological malignancies
Tetsutaro Hayashi1, Nobuyuki Hinata1
1Department of Urology, Hiroshima University Graduate School of Biomedical and Health Science, Hiroshima, Japan.
Abstract:
Antibody-drug conjugates represent a promising new treatment option that uses the targeting ability of an antibody to deliver cytotoxic drugs directly to tumors. Antibody-drug conjugates provide the opportunity to deliver drugs to antigen-expressing cancer cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows. To date, three antibody-drug conjugates have been approved by the US Food and Drug Administration, and many antibody-drug conjugates are under clinical development for urological malignancies. In this paper, we review the mechanism, history, and development of antibody-drug conjugates, and review the current landscape of antibody-drug conjugates in urological malignancies including 12 targets and 18 antibody-drug conjugates in prostate cancer, renal cancer, and urothelial cancer. Furthermore, we review the rational combination of antibody-drug conjugates with immune checkpoint inhibitors and consider future prospects to enhance the therapeutic activity of antibody-drug conjugates in urological malignancies.
Insights
Antibody-drug conjugates (ADCs) offer targeted cancer therapy by delivering cytotoxic drugs to tumors. This review explores ADCs in urological cancers, highlighting their potential and future development.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Antibody-drug conjugates (ADCs) are an emerging therapeutic class utilizing antibodies for targeted delivery of cytotoxic agents to cancer cells.
- ADCs aim to enhance efficacy and reduce systemic toxicity by exploiting antigen expression on tumor cells, thereby widening the therapeutic window.
- Three ADCs are FDA-approved, with numerous others in clinical trials for various malignancies, including urological cancers.
Purpose of the Study:
- To review the fundamental mechanisms, historical development, and current status of ADCs in oncology.
- To provide a comprehensive overview of the ADC landscape specifically within urological malignancies, encompassing prostate, renal, and urothelial cancers.
- To explore the synergistic potential of combining ADCs with immune checkpoint inhibitors and discuss future strategies for optimizing ADC therapy.
Main Methods:
- Literature review and synthesis of existing data on antibody-drug conjugates.
- Analysis of the current clinical development pipeline for ADCs in urological cancers, including identified targets and specific drug candidates.
- Examination of preclinical and clinical evidence for combination therapies involving ADCs and immune checkpoint inhibitors.
Main Results:
- The review details the mechanism of action and evolution of ADCs, noting their increasing significance in cancer treatment.
- A comprehensive analysis identified 12 targets and 18 ADCs currently under investigation for prostate, renal, and urothelial cancers.
- The potential for rational combinations of ADCs with immune checkpoint inhibitors is discussed, suggesting enhanced therapeutic outcomes.
Conclusions:
- ADCs represent a significant advancement in targeted cancer therapy, offering improved drug delivery to tumor sites.
- The field of ADCs in urological malignancies is rapidly expanding, with substantial ongoing research and development.
- Future directions focus on combination strategies, particularly with immune checkpoint inhibitors, to maximize the therapeutic benefit of ADCs in urological cancers.
