Drug metabolism by tumours: its nature, relevance and therapeutic implications.
Drug-metabolising enzymes (DMEs) are present in tumours and are capable of biotransforming a variety of antineoplastics. Tumoural drug metabolism is both a potential mechanism of resistance and a means of achieving optimal therapy. This review addresses the classes of DMEs, their cytotoxic substrates and distribution in specific malignancies. The limitations of preclinical and clinical studies are highlighted. Their role in predicting therapeutic response, the activation of prodrugs and the potential for their modulation for gain is also addressed. The contribution of tumoural DMEs to cancer therapy can only be ascertained through large prospective studies and supported by new technologies. Only then can efforts be concentrated in the design of better prodrugs or combination therapy to optimise individual therapy.
Michael
Michael
M
Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia. Michael.Michael@petermac.org
Doherty
Margaret M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase