Novel targeted cytotoxic chemotherapy for prostate cancer

This is one of three new fully-funded PhD studentships in the new Institute of Cancer Therapeutics Doctoral Training Centre (ICT-DTC) at the University of Bradford. Focused on the generation of new anticancer prodrugs, the ICT-DTC has been created following a major £2m investment by ICT spin-out company Incanthera Ltd.

Project Background
Taxanes (docetaxel, paclitaxel) are the single most important treatment for men with advanced prostate cancer, but consistently cause dose-limiting toxicities. There is, therefore, a need to develop novel strategies to optimise taxane therapy. Membrane-type matrix metalloproteinases (MT-MMPs) are functionally active at high levels in prostate cancer tissue, have negligible activity in normal tissue, and selectively cleave specific peptide sequences. In preliminary studies, we demonstrated proof-of-concept for an MT-MMP-activated taxane (paclitaxel) prodrug, ICT3205, in a prostate cancer model.

Aim
To develop a new non-toxic prodrug therapy for prostate cancer

Focus
Optimisation of our prototype prodrug, ICT3205. Fine-tuning of MT-MMP peptide sequence selectivity, and chemical modifications to enhance aqueous solubility. Evaluation of prodrug stability in normal tissues, prodrug activation in tumour tissues; MMP cleavage; assessment of aqueous solubility. Pilot pharmacokinetics study in mice for most promising compound.