Challenges of Cancer Drug Design A Drug Metabolism Perspective

Authors: Sanchez R.I.; Mesia-Vela S.; Kauffman F.C.

Source: Current Cancer Drug Targets, Volume 1, Number 1, May 2001 , pp. 1-32(32)

Publisher: Bentham Science Publishers

Abstract:

The time course and duration of action of drugs used in cancer chemotherapy are greatly influenced by the molecular and biochemical properties of enzymes associated with their metabolism. Variation in the response of individual patients to cancer chemotherapeutic agents is in large measure due to genetic and environmental factors that impinge on specific enzymes belonging to the two major classes of drug metabolizing enzymes. Current knowledge of the molecular biology and biochemistry of phase I drug metabolizing enzymes (cytochrome P450, flavin-containing and xanthine oxidases, NADPH quinone reductase, and aldehyde and dihydropyridine dehydrogenases), and phase II enzymes (glucuronosyl-, sulfo-, N-acetyl-, and glutathione transferases, and hydrolases) is reviewed briefly. Advances in understanding genetic and environmental factors that influence activities of phase I and phase II pathways of drug metabolism are discussed in the first sections of this review followed by a consideration of the influence of drug metabolism on the actions of agents currently used in the treatment of cancer. Emphasis is given to drugs that have recently been introduced into the armamentarium of cancer chemotherapy including inhibitors of chromatin function, target-based inhibitors of signal transduction and cyclin-dependent kinases, and angiogenesis inhibitors acting on metalloproteinases, epithelial cell growth, angiogenesis stimulation, and endothelial-specific integrins.

Keywords: Cancer Drug Design; cancer chemotherapy; NADPH quinone reductase; chromatin function; angiogenesis stimulation; antineoplastic; cynomolgus monkeys; Genetic Polymorphism; nutritional impairment; Cytochrome P450; fish malodor syndrome; Xanthine oxidase; Eniluracil; blood-brain barrier; Crigler-Najjar syndrome; DNA-binding drugs; BLM-hydrolase; Exatecan mesylate; Etoposide and teniposide; Matrix Metalloproteinases

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009013334296

Publication date: 2001-05-01

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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• In this Subject: Oncology ,  Pharmacology
• By this author: Sanchez R.I. ;  Mesia-Vela S. ;  Kauffman F.C.

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