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Antibody-drug conjugates in gynaecological cancers: opportunities and challenges
Kathleen N Moore1, Oladapo O Yeku2, Brooke E Howitt3
1Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. kmoore@gog.org.
Abstract:
Antibody-drug conjugates (ADCs) have transformed the cancer therapeutic landscape over the past two decades, profoundly shaping treatment outcomes across a wide array of indications. Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Current research priorities include identifying novel targets, better understanding mechanisms of resistance and sequencing strategies, and optimal management of the toxicities of ADCs. Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities.
Insights
Antibody-drug conjugates (ADCs) are revolutionizing gynecological cancer treatment, with three approved therapies. Future research focuses on new targets, resistance mechanisms, and combination strategies to improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) have significantly advanced cancer therapy over 20 years.
- Three ADCs are approved for gynecological cancers: mirvetuximab soravtansine (ovarian), trastuzumab deruxtecan (HER2+ solid tumors), and tisotumab vedotin (cervical).
Purpose of the Study:
- To review the current landscape of ADCs in gynecological malignancies.
- To highlight key advances and future opportunities in ADC development and application.
Main Methods:
- Literature review of approved ADCs and ongoing research in gynecological cancers.
- Analysis of current research priorities, including novel targets, resistance, toxicity management, and combination strategies.
Main Results:
- Established efficacy of mirvetuximab soravtansine, trastuzumab deruxtecan, and tisotumab vedotin in specific gynecological cancers.
- Identified research priorities: novel targets, resistance mechanisms, sequencing, toxicity management, and rational combinations.
Conclusions:
- ADCs represent a transformative therapeutic class in gynecological oncology.
- Future directions include exploring novel targets, understanding resistance, optimizing toxicity management, and combining ADCs with other therapies like immune checkpoint inhibitors to enhance antitumor immunity and response durability.
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