FR-alpha and B7-H4 Expression Found in Over 80% of Endometrial Cancer Cases, Supporting ADC Development
Key Insights
A retrospective study revealed significant expression of FR-alpha (82.5%) and B7-H4 (search) (82.1%) in endometrial cancer (search) samples, highlighting potential new therapeutic targets for antibody-drug conjugate development.
High B7-H4 (search) expression was predominantly found in low-grade endometroid disease, while elevated FR-alpha levels were more common in serous disease subtypes, suggesting distinct therapeutic approaches.
No tumor samples showed concurrent high expression of both FR-alpha and B7-H4 (search), with HER2 (search)-negative tumors more likely to exhibit low or medium expression of both markers.
New research from Duke University's School of Medicine has identified promising targets for antibody-drug conjugate (ADC) development in endometrial cancer (search), with data showing widespread expression of either folate receptor alpha (FRα (search)) or B7-H4 (search) in tumor samples.
The retrospective study, presented at the 2025 Society of Gynecologic Oncology Winter Meeting, analyzed tumor specimens from patients with advanced or recurrent endometrial cancer (search). The findings revealed that 82.5% of patient samples in the FRα (search) cohort (n=80) showed positive expression, with 10% demonstrating high expression levels. Similarly, in the B7-H4 (search) cohort (n=84), 82.1% of samples exhibited positive expression, with 28.6% showing high expression.
Expression Patterns Across Cancer Subtypes
The analysis encompassed various histologic subtypes, including low-grade endometrioid, high-grade endometroid, serous, clear cell, and carcinosarcoma. Notably, high FRα (search) expression was more prevalent in serous disease, while high B7-H4 (search) expression was significantly more frequent in low-grade endometroid disease (P = .01).
In a combined cohort analysis (n=42), researchers found that no tumor samples showed concurrent high expression of both FRα (search) and B7-H4 (search). HER2 (search)-negative tumors predominantly displayed low or medium expression of both markers (69.2%), compared to those with high expression of either FRα (15.4%) or B7-H4 (15.4%).
Clinical Outcomes and Survival Analysis
The study investigated potential correlations between marker expression and patient outcomes. For patients with high FRα (search) expression, the median progression-free survival was 2.4 months (95% CI, 1.0-not evaluable), compared to 2.9 months for those with low or medium expression. Overall survival showed similar patterns, with median survival of 7.5 months in the high-expression group versus 7.9 months in the low-to-medium-expression group.
Implications for Future Treatment Development
"Our study supports similar findings in literature with over 80% of endometrial cancer (search) specimens exhibiting either FRα (search) or B7-H4 (search) expression to some degree," stated Dr. Bobby May, gynecologic oncology resident at Duke University's School of Medicine. This high expression rate suggests these proteins could serve as valuable targets for ADC development, particularly significant given that no ADCs are currently FDA-approved for endometrial cancer treatment.
The research team emphasized the need for larger studies with standardized antibodies and expression definitions to confirm these findings. However, the current results provide strong support for pursuing ADC development in endometrial cancer (search), with potential for targeted approaches based on specific biomarker expression patterns.