Pre-Clinical Combination Targeting VEGF and PI3K in a Rare, Aggressive Mixed Endometrial Carcinoma: An Applied Case Report - PubMed
3 hours ago
- #Patient-Derived Organoids
- #Endometrial Carcinoma
- #PI3K-VEGF Combination
- A young patient with initially diagnosed grade 1 endometrioid endometrial cancer developed mixed aggressive carcinoma after endocrine treatment, featuring grade 1 endometrioid, large cell neuroendocrine, and undifferentiated histologies.
- Patient-derived organoid (PDO) OPTO.85 and organoid-derived xenograft (ODX) models were established from surgical specimens, with multi-omic analyses confirming they reflected the patient's tumor traits, including oncogenic alterations in PIK3CA, ARID1A, and CTNNB1.
- RNA-seq and ATAC-seq analyses revealed enrichment in VEGF and Wnt signaling pathways, suggesting therapeutic vulnerabilities, and a high-throughput drug screen showed sensitivity to PI3K inhibitors and responsiveness to VEGF inhibition.
- Cediranib (VEGF inhibitor) demonstrated synergy with BKM120 (PI3K inhibitor), significantly reducing organoid growth in vitro and suppressing tumor growth in vivo in the ODX model compared to single agents.
- The case exemplifies how genomic profiling and patient-derived models can identify actionable molecular changes in rare cancers with poor prognosis, supporting personalized therapy and clinical decision-making, pending prospective validation.