B7-H3 and c-MET in advanced prostate cancer: exploring possibilities of novel bi-specific drug development.

[PURPOSE] Prostate cancer (PCa) is a serious malignancy worldwide with the fifth highest mortality rate among tumors in males, and there are unmet clinical needs for PCa treatment. In this work, we aim to explore the expression and overlap between B7 Homolog 3 protein (B7-H3) and cell-surface receptor c-mesenchymal-epithelial transition factor (c-MET), to provide insight on B7-H3 and c-MET bi-specific ADC drugs development for advanced PCa.

[PATIENTS AND METHODS] In this retrospective cross-sectional study, formalin-fixed paraffin-embedded (FFPE) samples were analyzed from 135 male patients with advanced PCa at Hubei Cancer Hospital between 2019 and 2023. Biomarker and drug information were collected and used as major factors for patient stratification. Protein expression of B7-H3 (D9M2L) and c-MET (SP44) were determined by staining intensity and percent staining measurements. Positive expression of B7-H3 was defined as H Score ≥100, and positive expression of c-MET was defined as H Score >0. Historical medical information related to these cases were collected and the data were analyzed by R.

[RESULTS] 44% samples had both positive B7-H3 expression and c-MET expression, but c-MET expression is higher in peri-tumor sites than it in tumor site in PCa. The expression of B7-H3 and c-MET did not demonstrate significant correlation with age, metastatic site, or disease control rate (DCR). In addition, progression-free survival (PFS) of B7-H3 negative c-MET positive group was significantly shorter compared to the rest groups in patients receiving androgen deprivation therapy (ADT), while the expression of two markers was not significantly correlated with PFS in patients receiving ADT and new androgen receptor (AR) antagonists.

[CONCLUSIONS] In conclusion, B7-H3 is a promising drug developing target for PCa; however, c-MET may be limited by its low expression in tumor site while relative higher expression in peri-tumor site in PCa. Further investigation is warranted regarding bi-specific drugs for B7-H3 and another marker.