Ruud Brakenhoff is program leader within the Cancer Center of Amsterdam and professor in cancer genomics, particular in the field of head and neck squamous cell carcinomas (HNSCC). He studied medicine and was awarded his PhD at the Radboud University in Nijmegen, and is now heading the laboratory of Tumor Biology that belongs to the Department of Otolaryngology-Head and Neck Surgery of the VU University medical center in Amsterdam, The Netherlands. Research within the Department focuses on all aspects of head and neck cancer with the ultimate aim to improve diagnosis and treatment of this disease with grim prognosis. From own research activities ultrasound-guided fine needle aspiration cytology, sentinel node biopsy, FDG-PET and diffusion-weighted-MRI imaging as well as an HPV assay for oropharyngeal cancer have been implemented in routine clinical care. His research lines focus on oncogenesis and cancer genes, prognostic modeling, molecular diagnosis, and identification of novel drug targets.
1. Oncogenesis and cancer genes. HNSCC is classified in tumors caused by carcinogens (smoking and alcohol) and caused by human papillomavirus (HPV). HPV is most prevalent in oropharyngeal cancers and these HPV-positive oropharyngeal tumors have a very favorable prognosis. Research focuses on development of accurate assays for HPV detection, and clinical studies. Currently, the role of HPV in non-oropharyngeal tumors is investigated. Within the HPV-negative tumors a separate subclass of genetically-silent tumors has been identified that is now also studied in more detail. HNSCC arises in preneoplastic mucosal changes also coined as fields, which are sometimes visible as lesions, and based on previous molecular studies a patch-field-tumor progression model was postulated that it is now in the textbooks. The genes driving head and neck cancer are still intensively studied. Finally, the carcinogenesis in genetically predisposed patients such as those suffering from Fanconi anemia, is investigated.
2. Prognostic modeling and staging. The genetically distinct classes of HNSCC show a different prognosis. However, prognostic modeling is far from optimal and not useful for the individual patient. Multiparameter modeling including genomics and radiomics data is currently explored for most accurate prognostication and staging of the individual patient to personalize treatment. These studies include intratumoral molecular heterogeneity analyses, and investigations of the malignant squamous stem cell.
3. Molecular diagnosis. Since many year molecular assays have been explored at the laboratory to detect minimal residual cancer, and to predict recurrence and metastases at an early stage. In addition, several genetic assays have been developed and investigated to screen for preneoplastic mucosal changes using brushed samples, and to predict the risk for malignant transformation of these preneoplastic fields. Recently liquid biopsy approaches have been introduced including ctDNA and tumor-educated platelet profiling by next generation sequencing.
4. Identification of novel drug targets. The 5-years survival of HNSCC is 60%, and hardly increases. Novel treatments are therefore urgently awaited. Also the clinical management of preneoplastic mucosal changes is problematic as even resection or laser evaporation of visible lesions is not effective. HNSCC is not driven by activated oncogenes but by inactivated tumor suppressor genes that are not suited directly as drug targets. We therefore use functional genomics screens (siRNA, CRISPR-Cas9) to identify novel drug targets using the principals of synthetic and collateral lethality. Also siRNAs and microRNAs are explored as inhibiting drugs. To test efficacy in vivo both xenografted cell lines and PDX models are explored. The ultimate aim is to bring these novel treatments to the clinic.