FNA3 Precision Medicine Program - An integrated multi-layered approach to improve management of patients with Salivary Gland Malignancies

• Applicant: Dr. Julia Thierauf
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; Pathology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421845881

Rapid and accurate diagnosis of primary cancer, recurrence, and progression is a key focus in oncology because of its clinical and economic relevance. The diagnosis of salivary gland malignancies (SGM) is especially challenging due to the histological diversity of salivary gland lesions. Fine needle aspiration (FNA) cytology is often the first available specimen from salivary gland lesions. The broad spectrum of different histotypes of SGM poses significant challenges for cytopathologic recognition and the diagnostic clarification of “indeterminate” salivary gland FNAs often results in clinical uncertainty. Notably, routine next-generation sequencing (NGS)-testing has not been implemented into the diagnostic pathway of FNA and molecularly-informed surgery in SGM is currently not being performed. We hypothesize, that we can increase the sensitivity of an already established, rapid diagnostic tool by adding NGS to FNA and identify tumor-specific alterations in different SGM subsets. Therefore, we believe that optimizing FNA by supplementing NGS can significantly shorten time to definitive diagnosis and we can possibly assess time to initiation of appropriate and molecularly informed treatment. Moreover, we propose that our panel will facilitate an oncological relevant one step surgical procedure and an independent outcome measure might be a reduction of additional surgical procedures and costs. Furthermore, will focus on the clinical validation of a recently established NGS-panel for the detection and analysis of cell-free DNA. NGS-based analysis of cfDNA in plasma from SGM patients will hopefully provide a minimally invasive method to identify already established biomarkers in different SGM subtypes and measure them over time, ultimately aiming to monitor tumor evolution and resistance in real time. In addition, we are hoping to capture molecular and genetic heterogeneity in SGM by measuring changes in the mutational landscape and to possibly identify new genetic alterations for targeted therapy in peripheral blood samples. At present, no effective local or systemic treatment option for curative and first-line therapy is available for SGM patients beside radical tumor excision. Hence, SGM patients often are treated based on therapeutic modalities that show high rates of treatment failure. Our aim is to identify therapeutic targets and empower testing of candidate pharmacologic drugs, when SGMs recur. Therefore, we established a 3D-organotypic co-culture (OTC) model of different head and neck malignancies, including SGM. In case of treatment failure, the preclinical testing platform for recurrent SGM will directly integrate OTC-derived sensitivity data in the setting of individual response to second-line treatment. With this multi-stream project, we propose to leverage several innovative technologies to streamline progress in an integrated program.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Anthony John Iafrate, Ph.D.