Tyrosine kinase inhibitors: rationale, mechanisms of action, and implications for drug resistance.

Busse D, Yakes FM, Lenferink AE, Arteaga CL
Semin Oncol. 2001 28 (5 Suppl 16): 47-55

PMID: 11706396

Tyrosine kinases play a role in normal cellular regulatory processes. However, aberrant tyrosine kinase activity can lead to cellular transformation and can be causally associated with tumor maintenance and progression. In the last few years, high-throughput screening and the use of combinatorial, computational, and medicinal chemistry have led to the identification of small molecules that compete with the adenosine triphosphate binding site of the catalytic domain of several oncogenic tyrosine kinases. Some of these compounds are highly specific to a single tyrosine kinase, while others can inhibit several homologous kinase pockets simultaneously. At a practical level, the relative promiscuity of these inhibitors against more than one oncogenic tyrosine kinase may have clinical merit as well as implications for host tissue toxicity. Many of these small molecules are in different stages of preclinical and clinical development against several solid tumors and will be discussed.

Copyright 2001 by W.B. Saunders Company.

MeSH Terms (15)

Animals Antineoplastic Agents Breast Neoplasms Cell Cycle Clinical Trials as Topic Drug Evaluation, Preclinical Drug Resistance, Neoplasm Enzyme Inhibitors Humans Ligands Neoplasms, Glandular and Epithelial Protein-Tyrosine Kinases Receptor, ErbB-2 Receptor Protein-Tyrosine Kinases Signal Transduction

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