Signal transduction inhibitors in the treatment of breast cancer.
Signal transduction pathways are frequently altered in human breast cancer and are the targets of several novel therapies currently in clinical trials. Therapeutic strategies include extracellular blockade of tyrosine kinase receptors with the monoclonal antibodies C225 and trastuzumab. Competitive inhibitors of adenosine triphosphate binding sites on tyrosine and serine/threonine kinases are also being evaluated in phase I/II trials; these include ZD1839, OSI-774 and CI-1033. Flavopiridol and UCN-01 are nonspecific cell cycle kinase antagonists with preliminary evidence of breast cancer cell growth inhibition. Several inhibitors of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling are also in various stages of preclinical or clinical development. Additionally, inhibitors of farnesyl transferase have demonstrated activity in breast cancer cells irrespective of ras status. Current evidence suggests that targeting of signaling molecules is a promising new approach to treatment of breast cancer.
Nahta
Rita
R
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Hortobagyi
Gabriel N
GN
Esteva
Francisco J
FJ
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D051231:Farnesyltranstransferase; D005260:Female; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
D019883:Alkyl and Aryl Transferases; D000970:Antineoplastic Agents; D051231:Farnesyltranstransferase; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases