158 CHAPTER 6 GENERAL DISCUSSION Advanced cancer continues to be a heavy burden for society. In the Netherlands, 20% of patients who are diagnosed with cancer already have metastatic disease at the time of diagnosis1. Cancer metastases can also occur later in the course of the disease. Annually, around 38,000 patients in the Netherlands are diagnosed with metastatic cancer1. Only a minority of patients with metastatic disease can be cured with local therapies such as surgery or radiotherapy or sometimes curative systemic therapy strategies. For most of the patients with metastatic disease, palliative systemic treatment is their last resort, with the aim of disease- and symptom control and thereby prolongation of life while maintaining or improving their quality of life. Since cancer is a genetic disease, characterized by mutations and dysregulated protein kinase signaling2, protein kinases (and tyrosine kinases in particular) have become one of the most important drug targets in recent years3,4. Since the introduction of trastuzumab, a monoclonal antibody directed against ErbB25 in 1999 as the first targeted treatment, an increasing number of targeted anti-cancer drugs are annually approved by the FDA6. Together with the introduction of immune checkpoint inhibitors (ICI), protein kinase inhibitors (PKI’s) have made a powerful contribution to the improved survival of patients with advanced cancer7. This vast expansion of the targeted therapeutic arsenal broadens opportunities for patients with advanced cancer. One of the most important questions, which is under extensive evaluation, is how to select the right treatment for the right patient at the right time? What is the biomarker with the best predictive value for response (or resistance) to treatment? And what requirements need to be met before a targeted treatment strategy based on individual tumor characteristics can be offered to each patient with cancer? The studies in this thesis focus on clinical available pan-cancer genomics-based treatment selection in a drug repurposing clinical trial (chapter 2 and 3), the development of a phosphotyrosine proteomics selection method for a multi-targeted TKI (chapter 4) and the validation of a new liquid nitrogen-free snap freezer for optimal tissue handling to enable (multi)omics analysis on clinical samples (chapter 5). GENOMICS-BASED TREATMENT SELECTION; DRUG REDISCOVERY PROTOCOL Each tumor is unique in its genetic and molecular composition. With the improvement and wider implementation of next generation sequencing techniques, extensive molecular information from individual tumors has become available, often revealing unexpected genomic events. In 31% of patients with advanced cancer, an actionable genomic event was identified in the tumor DNA that predicted sensitivity to a targeted drug. In 13% of patients, a genomic target was identified for which targeted drugs are available, but not registered for the specific tumor type8.
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