Only recently, systemic anti-cancer treatment consisted of little more than chemotherapy, targeting mitosis in rapidly dividing cells such as cancer cells. Increasing biological insight has led to the development of more biology driven treatments, e.g. tyrosine kinase inhibitors and hormonal therapies. Still, not all patients benefit from anti-cancer treatment. This thesis comprises studies that aimed to personalize anti-cancer treatment based on intratumoral genetics and on pharmacokinetics of tyrosine kinase inhibitors