Antibody-drug conjugates as targeted therapy for treating gynecologic cancers: update 2025
Jordyn Silverstein1, Beth Karlan2, Nasim Herrington1
1Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA).
Purpose Of Review:
Provide the most up-to-date information on the dynamic landscape of antibody-drug conjugates (ADCs) in gynecologic cancers. We discuss the latest research that supports the approved ADCs and outline the ongoing trials and preliminary results that may lead to ADC approvals in the future. Current gaps in knowledge and areas for future research are discussed.
Recent Findings:
ADCs are rapidly changing the landscape of gynecologic cancer care. Three ADCs are currently FDA approved and used routinely in clinical practice, with many more currently in clinical development. The most common ADC target is folate receptor alpha of which there are 8 different folate receptor targeting ADCs in development. Other targets under investigation include trophoblast cell surface antigen-2 (Trop-2), claudin-6 (CLDN6), cadherin-6 (CDH6), nectin-4, HER-2 and B7-H4. ADCs can cause new and unique adverse effects, including ocular toxicities and interstitial lung disease.
Summary:
ADCs offer the opportunity for a more effective and personalized treatment approach for gynecologic cancer patients. Side effects must be closely monitored, and preventive measures must be followed to maximize benefit and minimize toxicity. A better understanding of the role of target proteins as biomarkers to predict response to ADCs will be critical for successful clinical implementation of ADCs and further research in this area is necessary.
Insights
Antibody-drug conjugates (ADCs) are transforming gynecologic cancer treatment with three FDA-approved options and many more in development. Close monitoring of unique side effects is crucial for patient benefit.
Area of Science:
- Gynecologic Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy.
- Their application in gynecologic cancers is rapidly evolving, offering new treatment paradigms.
Purpose of the Study:
- To provide an updated overview of ADCs in gynecologic cancers.
- To discuss current research supporting approved ADCs and future prospects.
- To identify knowledge gaps and future research directions.
Main Methods:
- Review of current literature on ADCs in gynecologic oncology.
- Analysis of data from approved ADCs and ongoing clinical trials.
- Discussion of emerging ADC targets and their preliminary results.
Main Results:
- Three ADCs are FDA-approved for gynecologic cancers, with numerous others in development.
- Folate receptor alpha is a common target, with eight ADCs in development.
- Investigational targets include Trop-2, CLDN6, CDH6, nectin-4, HER-2, and B7-H4.
- ADCs can induce unique toxicities, such as ocular and interstitial lung disease.
Conclusions:
- ADCs provide a personalized and effective treatment strategy for gynecologic cancer patients.
- Careful management of side effects is essential to optimize therapeutic benefits.
- Biomarker identification for predicting ADC response is critical for clinical success.
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