Our aim is to find oncogenic drivers and genetic markers for drug response in epithelial cancers utilizing different in vitro and ex vivo tumor models, clinical specimens and functional assays. Below you can find some information about the projects that are ongoing in the lab.
From cancer genomes to oncogenic drivers and drug targets
We have performed systematic genomic and transcriptomic profiling of multiple cancer cell lines and tumor samples to identify putative oncogenes and tumor suppressors whose expression is associated with genetic alterations. Especially, high-level amplifications have a clear impact on gene expression and these alterations are also associated with poor prognosis. We are interested in 11q13 amplification, which is one of the most commonly amplified regions in several epithelial cancers. Recently, we have studied the role of two genes, PPFIA1 and ANO1, encoding liprin-α1 and anoctamin 1, and found mechanistic insights how they contribute to cancer progression, cell adhesion and invasion in head and neck and breast carcinoma cell lines. For example, liprin-α1 is an essential protein in regulating focal adhesion dynamics, cell spreading and organization of cytoskeleton. We have recently found that liprin-α1 is a novel regulator of the tumor cell intermediate filament vimentin with differential oncogenic properties in actively proliferating or motile cells. Our main goal in these projects is to understand the molecular mechanisms by which genes activated by gene amplification contribute to oncogenic processes in cancer to find potential oncogenic drivers and molecular targets that could be targeted in combination with already existing therapies.
Biomarkers for drug sensitivity and resistance
The selection of targeted therapies based on mutation status have provided novel opportunities for cancer treatment. Our aim is to utilize a large collection of squamous cell carcinoma of head and neck (HNSCC) cell lines to identify biomarkers that associate to drug response of targeted agents. The only approved targeted agents for advanced HNSCC are cetuximab, a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), and recently, the immune checkpoint inhibitors nivolumab and pembrolizumab. There are no clinically approved biomarkers for therapy response for targeted agents. We have carried out a drug screening for genetically and clinically well-characterized HNSCC cell lines using FDA approved and investigational cancer drugs because testing large amount of drugs and their combinations in clinical trials is challenging. Our focus is on those specific genetic aberrations that associate with responses to inhibitors targeting signalling pathways that are under investigation in the treatment of head and neck cancer to uncover biomarkers for potential treatment and patients who benefit from the therapy.
Three-dimensional patient-derived in vitro models for head and neck cancer
Head and neck cancers encompass a group of tumors that are often aggressive in their biological behavior. There is a lack of effective therapies to treat patients who are not cured by surgery and/or (chemo)radiotherapy and lack of reliable in vitro models for therapy development. We are establishing novel platforms for modeling head and neck squamous cell carcinoma for drug testing, biomarker validation and molecular studies. In humans, tumors grow in a three dimensional (3D) environment in which their behavior is controlled through interactions with other cells and extracellular matrix. Therefore, we use patient-derived primary biopsy samples and different hydrogels to grow organoids, in vitro 3D cellular clusters derived from the primary tissue. Our aim is to find in vitro conditions that represent the original clinical head and neck tumor in regards of tumor heterogeneity, molecular profile, and drug responses. We are focusing on targeted agents using therapeutically exploitable pathways in human papilloma virus (HPV) negative head and neck cancer with currently few effective therapeutic options.