Characterization of EZH2 as a Therapeutic Target in Olfactory Neuroblastoma - A Combined Retrospective and Prospective Study

• Applicant: Privatdozent Dr. Constantin Hintschich
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549202461

Olfactory neuroblastoma is a rare, yet insufficiently studied tumor of the nasal cavity. Treatment is primarily carried out through surgery and adjuvant radiotherapy, and in rarer cases with primary chemotherapy. However, the significant side effects of surgical resection/radiotherapy and the poor prognosis after chemotherapy make the development of a targeted pharmacological therapy highly desirable. Recently, the methyltransferase EZH2 has been identified not only as a proliferation marker but also as a promising target for pharmacological therapy. The project proposal comprises two distinct study objectives: (i) EZH2 is to be retrospectively characterized as a prognostic marker of olfactory neuroblastoma. This objective seeks to explore the degree of correlation between EZH2 expression and individual patient prognosis through immunohistochemical analysis of archived tissue samples. (ii) Tazemetostat is an already ap- proved EZH2 inhibitor. In a prospective study objective, the effect of Tazemetostat will be evaluated in olfactory neuroblastoma tumoroids and in cell culture models. We anticipate that the results will provide insights into personalized tumor therapy of olfactory neuroblastoma, which may potentially be applied in clinical practice in the future.

• DFG Programme: Research Grants