Personalized medicine for patients with advanced cancer: Towards tailored anti-cancer treatment

The central theme of precision medicine is designing effective therapeutic interventions for individual patients. In the era of countless treatment options and rising healthcare costs, there is a clear and unmet need to ensure a satisfactory trade-off between quality of life, healthcare costs and treatment efficacy. Currently, many anti-cancer therapies are designed to neutralize the effect of a single genetic mistake detected in the DNA of cancer patients: so-called “targeted therapies”. Therefore, precision medicine in oncology has become nearly synonymous with DNA-sequencing. This is a rather one-dimensional approach to precision medicine and, as a consequence, most patient only marginally benefit from these novel treatment opportunities. A major reason for this is the context-dependency of oncogenic lesions among the thousands found in cancer genomes, and their significance for treatment outcome. Although problematic for targeted agents, this conceptual problem is even more pronounced for (combination) chemotherapies, because of their complex mechanisms of action.

Recent years have seen the adoption of novel technologies to study tumor biology, such as whole-genome sequencing and organoid culture. When cleverly combined with clinical studies and patient data, this creates an opportunity to approach the challenges of precision medicine from a new angle. In this thesis we confront the aforementioned challenges in several ways by integrative use of novel technologies, clinical studies and patient data, and propose several concepts to tailor anti-cancer treatment to individual patients.