PhD defence: Exploiting drug targets for development of rational combinations of classical and novel anticancer agents
PhD defence of J.J.J. Geenen
The past decennia anticancer treatment has been more and more individualized instead of treating a group of patients with the same malignancy equally. This more personalized treatment is based on the presence of specific tumor characteristics, patient characteristics or is tailored to the patient’s preference.
The aim of this thesis is to optimize anticancer treatment, based on specific patient and tumor characteristics. Four targets that can be present on patient tumor cells, which serve as target for treatment with anticancer medicine, are described in this thesis: PARP inhibition, Wee-1 inhibition, PD-L1 and Her2 inhibition. By giving a specific treatment focused on these targets, treatment will be more specific and individualized. In all targets, a combination of existing and new anticancer treatments are used in order to investigate the most effective and safe treatment option.
The clinical trials described in this thesis, investigate the optimal dosage in relation to toxicity. At the optimal dose level, there is sufficient efficacy with tolerable toxicity and therefore an acceptable quality of life. Besides the clinical studies, this thesis contains a review about PARP inhibition in a specific type of breast cancer and a review about Wee1 as a target for treatment. A paper about the application of PARP-inhibitors in patients with brain metastases is also included. With this thesis, a small step forward has been made in individualization of treatment instead of ‘one size fits all’