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Review
. 2025 Feb 24;14(5):333.
doi: 10.3390/cells14050333.

Development of Antibody-Drug Conjugates for Malignancies of the Uterine Corpus: A Review

Taro Yamanaka  1 , Tadaaki Nishikawa  2 , Hiroshi Yoshida  3
Affiliations
Review

Development of Antibody-Drug Conjugates for Malignancies of the Uterine Corpus: A Review

Taro Yamanaka et al. Cells. .

Abstract

Despite recent advances in cancer treatment, the prognosis for uterine malignancies (carcinoma and sarcoma) requires further improvement. Antibody-drug conjugates (ADCs) have emerged as a novel class of anti-cancer therapeutic agents, and multiple ADCs have been approved for other types of cancer. In 2024, trastuzumab deruxtecan received approval from the US Food and Drug Administration for cancer types and became the first ADC approved for the treatment of uterine malignancies. Many ADCs are currently being investigated in uterine malignancies, and therefore, there is a need to gain a deeper understanding of ADCs. In this article, we aim to provide a comprehensive overview of the advancements in ADCs. The contents of this article include the structure and mechanism of action, an analysis of recent clinical trials, and expected future clinical questions. This article also focuses on uterine sarcoma, which is not often highlighted as a target for ADC treatment.

Keywords: AXL; B7-H3; B7-H4; FR?; HER2; TROP2; antibody–drug conjugate; endometrial carcinoma; uterine carcinosarcoma; uterine sarcoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histological and Molecular Features of Endometrial Carcinomas. Representative histopathological images illustrating the key histological subtypes of endometrial carcinoma, including endometrioid, serous, clear cell, carcinosarcoma, undifferentiated/dedifferentiated, and mesonephric-like carcinoma. Relevant molecular alterations associated with each subtype are also highlighted.
Figure 3
Figure 3
Histological and Molecular Features of Uterine Sarcomas. Representative histopathological images illustrating the key histological subtypes of uterine sarcoma, including leiomyosarcoma, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, PEComa, and adenosarcoma. Relevant molecular alterations associated with each subtype are also highlighted.
Figure 2
Figure 2
The TCGA-surrogate approach of molecular classification of endometrial carcinoma. Schematic representation of the TCGA-surrogate approach for molecular classification of endometrial carcinomas. The four molecular subtypes—POLE-mutant (POLE), mismatch repair-deficient (MMRd), p53-abnormal (p53abn), and non-specific molecular phenotype (NSMP)—are depicted.
See this image and copyright information in PMC

References

    1. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. doi: 10.3322/caac.21708. - DOI - PubMed
    1. Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C.H., Rabaglio M., Marme F., Marth C., et al. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): A randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024;25:1135–1146. doi: 10.1016/S1470-2045(24)00334-6. - DOI - PubMed
    1. Eskander R.N., Sill M.W., Beffa L., Moore R.G., Hope J.M., Musa F.B., Mannel R., Shahin M.S., Cantuaria G.H., Girda E., et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N. Engl. J. Med. 2023;388:2159–2170. doi: 10.1056/NEJMoa2302312. - DOI - PMC - PubMed
    1. Makker V., Colombo N., Casado Herraez A., Santin A.D., Colomba E., Miller D.S., Fujiwara K., Pignata S., Baron-Hay S., Ray-Coquard I., et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N. Engl. J. Med. 2022;386:437–448. doi: 10.1056/NEJMoa2108330. - DOI - PMC - PubMed
    1. Marabelle A., Le D.T., Ascierto P.A., Di Giacomo A.M., De Jesus-Acosta A., Delord J.P., Geva R., Gottfried M., Penel N., Hansen A.R., et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J. Clin. Oncol. 2020;38:1–10. doi: 10.1200/JCO.19.02105. - DOI - PMC - PubMed

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