The pharmacological evaluation and development of novel anti-cancer compounds

The work presented in this thesis represents my ‘adventures’ in the field of cancer pharmacology and drug development. The work has been segregated into six major themes that represent my interests over a career spanning 30 years. These themes are; (i) the preclinical and clinical development of EO9 (Apaziquone) as a loco-regional therapy for non-muscle invasive bladder cancer (ii) the microenvironment of cancer, cancer metabolism and the pharmacological evaluation of enzyme activated bioreductive drugs (iii) individualising chemotherapy and personalized medicine (iv) the pharmacological evaluation of synthetic organic compounds and natural products (v) the pharmacological evaluation of inorganic complexes and (vi) drug delivery and in silico modelling studies. A total of 109 peer reviewed research publications are presented together with 12 review articles, the majority of which have also been peer reviewed. Also included is an impact case study report for the Research Excellence Framework 2014 submission which highlights one area of my research that has had direct impact upon the health and well-being of cancer patients, namely the development of Apaziquone (EO9) as an intravesical therapy for superficial bladder cancer. Working in the field of anti-cancer drug development is inherently multidisciplinary and I hereby wish to acknowledge and thank the contributions of colleagues and students without whom, this thesis would not have been possible.