Beyond Herceptin and Gleevec.
Identification of the key role of protein kinases as potential oncoproteins has led to the emergence of a new era of target-directed therapies. Among a variety of novel therapeutic strategies two have shown the most promise and led to a variety of therapeutic agents in clinical development. One approach utilises humanised monoclonal antibodies generated against the extracellular domain of transmembrane protein kinases. The second approach is the generation of small molecule ATP analogues targeting the kinase domain itself. The approval of agents such as Herceptin for the treatment of advanced breast cancer and Gleevec for chronic myelogenous leukemia and gastrointestinal stromal tumours are the first examples of gene-based cancer drugs and represent the first example of a novel strategy in anti-cancer therapy.
Fischer
Oliver M
OM
Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, D-82152 Martinsried, Germany.
Streit
Sylvia
S
Hart
Stefan
S
Ullrich
Axel
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D002453:Cell Cycle / Q000187:drug effects; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D000068877:Imatinib Mesylate; D020928:Mitogen-Activated Protein Kinases; D010879:Piperazines; D011743:Pyrimidines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000068878:Trastuzumab