Our group aims to
It has previously been shown that the neural crest transcription factor SOX10 is a therapeutic target in melanoma. We are currently exploring approaches to suppress SOX10 pharmacologically (PI Dr. Olga Shakhova), using mass spectrometry (MS)-based approaches. CCSA is closely related to melanoma, since its cell of origin is also neural crest derived. We are therefore exploring whether those therapeutic strategies can be expanded to CCSA.
In a second approach, we have performed an in vitro high-throughput screen to identify novel compounds with potential therapeutic efficacy in CCSA and are currently validating the results in vitro and in vivo in patient-derived xenograft (PDX) mouse models of CCSA. We will also investigate the involved downstream signalling pathways using in vitro kinase screens and MS.
In close collaboration with Prof. Beat Schäfer and Dr. Marco Wachtel, University Children’s Hospital, we are setting up an ex vivo drug screening platform on patient-derived tumoroids. This approach has been successfully applied by Prof. Schäfer and his team in paediatric rhabdomyosarcomas and we now aim to expand this platform to adult patients with soft tissue and Ewing sarcomas.
In a tumor-agnostic translational study on patients with malignant effusions, we are performing ex vivo single-cell drug screening using automated microscopy (called ‘pharmacoscopy’), in close collaboration with Prof. Berend Snijder, Institute of Molecular Systems Biology, ETH Zurich, who co-developped this technique. Drug screens using pharmacoscopy have the advantage of read-outs at single-cell levels and can distinguish between responses in cancer versus normal cells in the same sample. This permits to calculate an on-target and off-target response and increases the predictive value of the screens, compared to population-averaged (global) read-outs. Moreover, we plan to expand this approach to tumor biopsies from patients with sarcomas.
Oberarzt Onkologie, Klinik für Medizinische Onkologie und Hämatologie
Co-Leiter Sarkomzentrum, Comprehensive Cancer Center Zürich