The evolving landscape of antibody-drug conjugates in gynecologic cancers
Anthony Tolcher1, Erika Hamilton2, Robert L Coleman3
1NEXT Oncology, 2829 Babcock Road Suite 300, San Antonio, TX 78229 United States.
Abstract:
Despite significant advances in the treatment of cervical, ovarian, and uterine cancers with the approvals of checkpoint and PARP inhibitors into standard treatment, patients with recurrent metastatic gynecologic malignancies still experience poor outcomes, and most of these patients will experience disease relapse. Once standard preferred treatments are exhausted, options have historically been limited to treatments associated with poor outcomes and notable toxicities. Consequently, novel therapies that are effective and well-tolerated are needed for patients with recurrent and metastatic gynecologic malignancies. Antibody-drug conjugates (ADCs) are a class of targeted therapies that are well established in several cancers including hematologic malignancies and some solid tumors. Significant strides in ADC technology and design have led to improvements in efficacy and safety with newer-generation ADCs. Consequently, ADCs are gaining traction in gynecologic cancers with the recent US Food and Drug Administration approvals of tisotumab vedotin in cervical cancer and mirvetuximab soravtansine in ovarian cancer. Many additional ADCs against various targets are being explored in patients with metastatic or recurrent gynecologic malignancies. The purpose of this review is to summarize the nuanced structural and functional properties of ADCs, while outlining opportunities for innovation. Further, we highlight the ADCs in clinical development for gynecologic malignancies, exploring how ADCs may be able to address the clinical care gap for patients with gynecologic cancers.
Insights
New antibody-drug conjugates (ADCs) offer improved treatments for recurrent gynecologic cancers. These targeted therapies show promise for patients with advanced cervical, ovarian, and uterine cancers when standard options fail.
Area of Science:
- Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Recurrent metastatic gynecologic malignancies (cervical, ovarian, uterine) have poor outcomes despite advances like checkpoint and PARP inhibitors.
- Limited effective and well-tolerated treatment options exist for patients with exhausted standard therapies.
- Antibody-drug conjugates (ADCs) are an emerging class of targeted therapies with demonstrated efficacy in various cancers.
Purpose of the Study:
- To review the structural and functional properties of antibody-drug conjugates (ADCs).
- To outline opportunities for innovation in ADC development for gynecologic cancers.
- To highlight ADCs in clinical development for gynecologic malignancies and their potential to address unmet clinical needs.
Main Methods:
- Review of current literature on antibody-drug conjugate technology and its application in gynecologic oncology.
- Analysis of recent FDA approvals and ongoing clinical trials of ADCs in cervical, ovarian, and uterine cancers.
- Exploration of ADC mechanisms of action, design improvements, and safety profiles.
Main Results:
- ADCs represent a significant advancement in targeted cancer therapy, with newer generations showing improved efficacy and safety.
- Recent approvals of tisotumab vedotin (cervical cancer) and mirvetuximab soravtansine (ovarian cancer) underscore ADC potential in gynecologic cancers.
- Numerous ADCs targeting various antigens are under investigation for recurrent and metastatic gynecologic malignancies.
Conclusions:
- Antibody-drug conjugates are a promising therapeutic strategy for patients with recurrent and metastatic gynecologic cancers.
- Continued innovation in ADC design and target selection may further improve outcomes for this patient population.
- ADCs have the potential to fill a critical clinical care gap in advanced gynecologic malignancies.
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