Tyrosine kinase inhibitors: why does the current process of clinical development not apply to them?

Arteaga CL, Baselga J
Cancer Cell. 2004 5 (6): 525-31

PMID: 15193255 · DOI:10.1016/j.ccr.2004.05.028

The robust clinical activity of imatinib and trastuzumab for treatment of chronic myeloid leukemia, gastrointestinal stromal tumors, and breast cancer has demonstrated that blocking pathogenic tyrosine kinases can alter the natural history of human tumors. On the other hand, EGF receptor inhibitors have shown overall modest activity. The contrast in the development of these agents implies that both molecular target dependence and patient selection are essential for the successful outcome of this process. We will contrast lessons derived from the development of inhibitors of Abl, c-Kit, HER2/neu (erbB2), and EGFR, highlight successes and limitations in the field, and propose new approaches for clinical development of tyrosine kinase inhibitor therapy.

MeSH Terms (18)

Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Benzamides Cell Line, Tumor Clinical Trials as Topic Enzyme Inhibitors ErbB Receptors Humans Imatinib Mesylate Leukemia, Myelogenous, Chronic, BCR-ABL Positive Mutation Oncogene Proteins v-abl Piperazines Protein-Tyrosine Kinases Proto-Oncogene Proteins c-kit Pyrimidines Receptor, ErbB-2 Trastuzumab

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