NOVEL THERAPY FOR BRAIN METASTASIS

Despite research advances, cancer still remains a major life threat with increasing societal burdens. Previously, the theragnostic laboratory at KU Leuven has developed an ingenious small molecule dual targeting pan-anticancer theragnostic strategy called OncoCiDia, which combines tumor necrotizing effect by using a vascular disrupting agent such as Combretastatin A-4 phosphate (CA4P) and targeted radiotherapy by using a necrosis-avid compound such as Hypericin labeled with radioactive iodine-131 (131I-Hyp). OncoCiDia is primarily considered as a palliative care to patients with late-stage disease. However, our recent findings suggest that under certain conditions this palliative OncoCiDia could become a curative dual-targeting chemoradioablation method to eradicate all solid cancers especially at their "micro-tumor" stage. To further explore the efficacy, safety and mechanism of this method and provide experimental evidence for later clinic use, the research topic of my PhD is proposed. Under supervisions of my promoters and with our well-established imaging-navigated translational research platform, this doctoral study will be conducted by performing the in vivo and in vitro experiments covering the aspects of 1) therapeutic efficacies, 2) mechanisms of actions and 3) safety considerations, in order to achieve evidenced data and conclusions. Specifically, in vivo experiments in tumour (carcinomas, adenomas and sarcomas) models of different animal (mice, rats and rabbits) species will be performed involving multiparametric imaging modalities and postmortem histopathology. To further explore the mechanisms behind the super-efficacy of CA4P in micro-cancers and the avidity of 131I-Hyp to tumour necrosis, in vivo, ex vivo and in vitro experiments and dosimetry calculations will be also carried out. In short, this doctoral research may demonstrate that OncoCiDia could be particularly effective to small solid malignancies.

Publication year:2022

Accessibility:Closed