Endometrial Cancer PDX Model – EC6
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Model Overview
Model Details
- Model: Endometrial Cancer PDX Model – EC6
- Animal: NSG Mice
- Weight: 18-22 g
- Passage: P3 (stable)
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- Cancer Type: Endometrial Dedifferentiated Carcinoma
- Age: 6-8 Weeks
- Molecular Profile: dMMR (MLH1/PMS2-deficient), MLH1 Promoter Methylation+, p53 Wild-type, ER/PR Patchy Positive.
- Matched PDC Model: PDC-EC6
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Patient Information
- Sex: Female
- Race/Ethnicit: /
- Age at Diagnosis: 73 years
- BMI: 38.77
- Diagnosis: Dedifferentiated carcinoma, Grade 3, Stage IIIB (initially diagnosed as Stage IVB poorly differentiated uterine cancer)
- Treatment History: Received 3 cycles of neoadjuvant chemotherapy (Carboplatin/Taxol) prior to sample collection; post-surgery chemotherapy + immunotherapy (Carboplatin/Taxol/Pembrolizumab)
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Molecular Characterization
Immunohistochemistry (IHC) Profile
- ER: Patchy positive
- PR: Patchy positive
- p53: Wild-type
- p16: Focally positive
- MLH1: Not expressed (loss in tumor cells)
- PMS2: Not expressed (loss in tumor cells)
- MSH2: Intact
- MSH6: Intact
- BRG1: Retained
- PAX8: Negative (in dedifferentiated areas)
- Pan-Keratin: Negative (in dedifferentiated areas)
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 Fig. 1 ER and PR expression in PDX-EC6 model. (Source: Alfa Cytology) |
Molecular Classification
- MMR Status: Deficient (dMMR) – MLH1/PMS2 loss
- MLH1 Promoter Methylation: Positive
- p53 Status: Wild-type
- ER/PR Status: Patchy positive
- MSI Status: MSI-H (inferred from dMMR)
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Genetic Testing
- CancerNext + RNAinsight testing revealed no mutations, variants, or gross deletions detected across the 36 genes analyzed, including BRCA1/2, MLH1, MSH2, MSH6, PMS2, PTEN, TP53, POLE, and other key cancer-related genes.
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Patient Clinical History – Diagnosis and Treatment Timeline
- Nov 16, 2022: CA-125: 38; Serum calcium: 10.1; Glucose: 135
- Nov 18, 2022: Initiation of neoadjuvant chemotherapy Cycle 1: Carboplatin/Taxol
- Jan 3, 2023: Cycle 3: Carboplatin/Taxol (effective in reducing tumor size); CA-125: 23; Serum calcium: 9.6; Glucose: 132
- Jan 17, 2023: PET/CT: Significant reduction in endometrial mass and vaginal tumor; resolution of pulmonary nodules; residual left paraaortic lymph node
- Jan 24, 2023: Serum calcium: 9.6
- Jan 27, 2023: Sample receipt date; Serum calcium: 8.9
- Jan 28, 2023: Glucose: 182
- Post-surgery: Surgical resection + Chemotherapy/Immunotherapy (Carboplatin/Taxol + Pembrolizumab)
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Case Study: PDX-EC6 – HDAC Inhibitor-Enhanced Hormonal Therapy
Progesterone receptor (PR) downregulation is a key mechanism underlying endocrine resistance in endometrial cancer, and PR expression can be restored through epigenetic modulation via HDAC inhibitors.The PDX-EC6 model, derived from a 73-year-old patient with Stage IIIB dedifferentiated endometrial carcinoma (ER/PR patchy positive, dMMR), represents an ideal platform for evaluating the efficacy of HDAC inhibitors in combination with progestin therapy.
In this study, PDX-EC6 tumor-bearing mice were divided into four groups: vehicle control, MPA monotherapy (1 mg/mouse, i.m.), entinostat monotherapy (0.3 mg/mouse, p.o.), and the combination group. Tumor growth inhibition was assessed across groups to evaluate the synergistic anti-tumor effects of the combination regimen.
Result:
- Inhibition of tumor proliferation: Entinostat significantly suppressed tumor growth in PDX-EC6.
- Restoration of PR expression: Entinostat restored PR expression through transcriptional de-repression.
- Synergistic anti-tumor efficacy: The MPA + entinostat combination demonstrated superior tumor growth inhibition compared to either monotherapy.
Fig. 2 Tumor growth curves and tumor weight. Data are presented as mean ± standard error (SEM). (Source: Alfa Cytology)
Conclusion:
The PDX-EC6 model successfully validated the strategy of HDAC inhibitor (entinostat)-mediated epigenetic restoration of PR expression and enhancement of progestin therapy efficacy. The MPA plus entinostat combination demonstrated synergistic anti-tumor activity in vivo, providing robust preclinical evidence for overcoming endocrine resistance in endometrial cancer.
Accelerate Your Endometrial Cancer Drug Development
From model establishment to preclinical validation, Alfa Cytology provides PDX models with comprehensive molecular characterization and pharmacodynamic validation. Whether you are exploring novel immunotherapies, combination strategies, or screening effective drug candidates, our models deliver reliable preclinical data to support your research programs. Please don't hesitate to contact us to discuss your specific needs.
For research use only.
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