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An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells
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Endocrine Therapy for Endometrial Carcinoma: Current Evidence, Resistance Mechanisms, and Biomarker-Driven Patient

Taro Yamanaka1, Hiroshi Yoshida2, Tatsunori Shimoi1

  • 1Department of Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.

Current Oncology (Toronto, Ont.)
|February 26, 2026
PubMed

Insights

Endometrial carcinoma treatment is shifting to precision medicine. Novel combination endocrine therapies, including targeted agents, show promise for improving outcomes, especially in specific molecular subgroups.

Area of Science:

  • Gynecologic Oncology
  • Precision Medicine
  • Molecular Pathology

Background:

  • Endometrial carcinoma (EC) treatment is evolving from traditional histology to molecular classification (Cancer Genome Atlas - TCGA).
  • The "No Specific Molecular Profile" (NSMP) subgroup represents a significant portion of EC cases and is a key target for endocrine therapy (ET).
  • While ET is established, its monotherapy efficacy is limited, necessitating exploration of novel strategies.

Purpose of the Study:

  • To review current and emerging endocrine strategies for endometrial carcinoma.
  • To highlight the role of combination therapies and targeted agents in overcoming ET resistance.
  • To discuss the importance of molecular biomarkers for patient selection in precision oncology.

Main Methods:

  • Comprehensive literature review of endocrine therapies and molecular classifications in EC.
  • Analysis of recent clinical trial data on combination therapies (e.g., CDK4/6, mTOR inhibitors).
  • Discussion of predictive biomarkers and next-generation agents like selective estrogen receptor degraders (SERDs).

Main Results:

  • Combination therapies integrating molecularly targeted agents significantly improve clinical outcomes in EC.
  • Patients with TP53 wild-type and CTNNB1 mutations show remarkable response to these novel combinations.
  • Next-generation SERDs and refined biomarker strategies hold potential for enhanced patient selection.

Conclusions:

  • Endocrine therapy is transitioning into a cornerstone of precision oncology for advanced or recurrent EC.
  • Molecular insights are driving personalized treatment approaches, moving beyond traditional palliative roles.
  • Combination endocrine-based strategies offer a more effective and personalized treatment paradigm for EC.
Keywords:
CDK4/6 inhibitorendocrine therapyendometrial cancerestrogen receptormTOR inhibitorprogesterone receptorprogestinselective estrogen receptor degraders

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