Drug metabolism by tumours: its nature, relevance and therapeutic implications

Abstract

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.

Keywords::

• cancer
• chemotherapy
• drug-metabolising enzymes
• tumoural drug metabolism