Biomarker-driven treatment strategies in solid tumors: Insights from clinical and translational research

Abstract

Over the past two decades, significant progress has been made in the treatment of certain tumor types with specific characteristics, such as gene mutations. As a result, several novel targeted therapies have been approved for the treatment of various tumor types and yielded promising results. However, the emergence of therapy resistance (unresponsiveness of the tumor cells to therapy) limits the clinical effectiveness of many anticancer drugs. The aim of the research described in this thesis was to determine the anticancer activity of different treatment strategies targeting specific tumor characteristics in various solid tumors, known as biomarker-driven treatments. The ultimate goal is to optimize the treatment of these tumors to improve the survival of the described patient populations. An example of a tumor cell characteristic that can be used as biomarker for the treatment of a certain tumor type is an activated signaling pathway that the tumor uses to proliferate and to evade the given treatment. Inhibiting these signaling pathways using targeted drugs is a strategy that can be employed to counteract tumor growth. The safety and clinical activity of this treatment strategy in different tumors with various characteristics are discussed in this thesis. In addition to inhibition of tumor growth through targeted treatments, the effect of these treatments on tumor characteristics is also addressed. In the described clinical trials, tumor material is collected to examine potential differences in tumor characteristics before and after the study treatment. These data is among others crucial for the refinement of patient selection in future studies.