Efficacy of targeted therapy and modeling androgen-receptor/HER2 signal pathways in preclinical salivary duct carcinoma models

• Applicant: Dr. Marcel Mayer
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539250008

Objective 1 is to test the hypotheses that (1) AR and HER2 pathways have salivary gland cell-specific downstream effects with crosstalk between these two pathways, and that (2) the efficacy of antiandrogen therapy is testosterone-dependent in salivary duct carcinoma (SDC). We will perform comprehensive proliferation and transcriptomic experiments in SDC patient-derived xenograft (PDX) models with differing HER2 and AR expression to further characterize and understand the tumor-intrinsic and microenvironmental effects of AR and HER2 activation. This basic understanding of AR and HER2 pathways in SDC cells is crucial for the development of more effective therapeutic strategies. Objective 2 is to characterize the extent and intensity of expression of Trop-2, Mucin-1, and CD138 in the existing SDC PDXs and to examine the efficacy of sacituzumab govitecan, AS140, and indatuximab ravtansin in these preclinical models. The proof of in vivo antitumor efficacy will provide the basis for first clinical studies of these drugs in patients with SDC.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Luc Morris, Ph.D.