Possibilities of Targeted Therapies for Brain Metastasis

Abstract

In the era of therapies successfully targeting distinct molecular pathways in cancer, the incidence and relevance of brain metastases are rising. Generally, the old therapeutic nihilism with respect to brain metastasis has given way to a more pragmatic approach, aiming to optimally combine (radio)surgery, whole brain radiotherapy, and sometimes systemic chemotherapy. However, local approaches inevitably fail to address the multifocal nature of the disease, whole brain radiotherapy shows relevant neurotoxicity, and systemic chemotherapy faces the obstacle of the blood-brain/tumor-barrier. Therefore, judicious addition of targeted agents to the therapeutic armamentarium for brain metastases holds the promise to make a real difference for patients suffering from this devastating disease. Unfortunately, because of their unfavorable prognosis, patients with brain metastases have traditionally been excluded from studies with targeted therapies. This is changing now for several reasons, making it likely that we will obtain relevant clinical data in the next few years. The following chapter gives an overview of new therapies targeting molecular pathways both in the tumor stroma and in cancer cells, covering its theoretical and reported activity against brain metastases. A special emphasis will be placed on prophylaxis, i.e. prevention of macrometastasis formation.