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Review
. 2023 Nov 2;28(21):7389.
doi: 10.3390/molecules28217389.

Antibody-Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors

Blair McNamara  1 , Michelle Greenman  1 , Nicole Pebley  1 , Levent Mutlu  1 , Alessandro D Santin  1
Affiliations
Review

Antibody-Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors

Blair McNamara et al. Molecules. .

Abstract

Antibody-drug conjugates (ADCs) are a new class of targeted anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a highly cytotoxic molecule payload bonded through specifically designed cleavable or non-cleavable chemical linkers. One such tumor surface receptor is human epidermal growth factor 2 (HER2), which is of interest for the treatment of many gynecologic tumors. ADCs enable the targeted delivery of a variety of cytotoxic therapies to tumor cells while minimizing delivery to healthy tissues. This review summarizes the existing literature about HER2-targeting ADC therapies approved for use in gynecologic malignancies, relevant preclinical studies, strategies to address ADC resistance, and ongoing clinical trials.

Keywords: ERBB2; HER2; antibody–drug conjugate; cervical cancer; chemotherapy; endometrial cancer; gynecologic malignancy; ovarian cancer.

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Conflict of interest statement

A.D.S. reports grants from PUMA, grants from IMMUNOMEDICS, grants from GILEAD, grants from SYNTHON, grants and personal fees from MERCK, grants from BOEHINGER-INGELHEIM, grants from GENENTECH, grants and personal fees from TESARO, and grants and personal fees from EISAI. L.M. reports consulting fees from Ethicon. The remaining authors have no conflict of interest.

Figures

Figure 1
Figure 1
General structure of an antibody–drug conjugate.
Figure 2
Figure 2
Core ADC mechanism of action.
Figure 3
Figure 3
Fc-receptor-mediated antibody-dependent cellular cytotoxicity.
Figure 4
Figure 4
HER2 expression in normal cells vs. overexpression in malignant cells. (HER2 overexpression determined by immunohistochemistry (IHC) staining of 2+/3+ or fluorescence in situ hybridization assays (FISH) gene amplification).
Figure 5
Figure 5
Possible mechanisms of resistance to HER2 ADCs.
See this image and copyright information in PMC

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