Fully-funded PhD studentships at The Institute of Cancer Therapeutics Doctoral Training Centre - Novel targeted cytotoxic chemotherapy for colorectal 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.

We are now looking for applications from outstanding potential PhD candidates.

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Project

Novel targeted cytotoxic chemotherapy for colorectal cancer.

Background

Metastatic colorectal cancer (CRC) is largely incurable by conventional approaches and requiring the development of better therapeutics. Clinical studies indicate that increased levels of an enzyme known as cytochrome P450 2W1 (CYP2W1) positively correlate with the degree of tumour malignancy, as well as with decreased 10-year survival in patients with CRC.

We have developed prodrugs of the duocarmycin family of natural products and shown in proof-of-concept studies that a lead prodrug (ICT2706) is selectively activated in CRC in vitro and in vivo. 

Aim

To develop a new non-toxic prodrug therapy for colorectal cancer.

Focus

Re-engineering of the duocarmycin scaffold through design and synthetic manipulations to discover novel prodrugs with clinical potential. Compounds with high affinity for CYP2W1 will be co-crystallised with the enzyme to provide mechanistic insight into the active site and function of the enzyme. Lead prodrug will be investigated in an appropriate in vivo CRC model.

Relevant papers

• Travica S. et al., Clin. Cancer Res. 2013, 19(11), 2952-61
• Sheldrake H.M. et al., J. Med. Chem. 2013, 56(15), 6273-7
• Ghosh N. et al., Curr. Top. in Med. Chem. 2009, 9(16), 1494-524