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High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options

  • Gynecologic Oncology: Review (Invited)
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Although many recent advancements have been made in women’s health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease. Recent early phase trials suggest that regardless of subtype, combination therapy with agents that have distinct mechanisms of action is a fruitful approach to the treatment of high-grade EnCa. Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

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All references acknowledged were readily obtainable from PubMed.

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Funding

BRR and OOY are supported in part by the Nile Albright Research Foundation (NARF). BRR is supported in part by the Vincent Memorial Hospital Foundation (VMHF).

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Authors and Affiliations

  1. Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, 60 Blossom St, 02114, Boston, MA, USA

    Yusuke Matoba, William B. Manning, Varvara Mazina, Oladapo O. Yeku & Bo R. Rueda

  2. Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, 02115, Boston, MA, USA

    Yusuke Matoba, William B. Manning, Varvara Mazina & Bo R. Rueda

  3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, 02114, Boston, MA, USA

    William B. Manning & Varvara Mazina

  4. Department of Pathology, Massachusetts General Hospital, 021151, Boston, MA, USA

    Kyle M. Devins

  5. Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, 02115, Boston, MA, USA

    Lara Milane

  6. Cancer Center, Massachusetts General Hospital, 55 Fruit St, 02114, Boston, MA, USA

    Oladapo O. Yeku

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O.O.Y reports grants from Ascendis Pharma A/S, Avenge Bio, Inc., Immunocore Limited, Duality Biologics, Merck Sharp & Dohme Corporation, Pionyr Immunotherapeutics Inc., ProfoundBio, and the Department of Defense. Consulting fees from Celldex Therapeutics, GIMV NV, TigaTx Inc. Advisory board role at hC Bioscience. In addition, he has a patent pending for MUC16 Directed Antibodies for therapeutic applications, and a patent pending for Human Artificial Chromosomes for therapeutic applications. None of these disclosures have no direct relevance on the current review. B.R.R. reports serving on the advisory board for VincenTech and does not have a direct bearing to the current review. All other authors declare no COI related to this review.

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Matoba, Y., Devins, K.M., Milane, L. et al. High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01544-5

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