Receptor-targeted cancer therapy.
Insight into the molecular mechanisms of malignant transformation is changing the way cancer is being treated. Conventional treatment strategies target the DNA of all dividing cells, resulting in a significantly increased risk of collateral toxicity. In addition, the accumulation of multiple mutations leads to drug resistance in many cancer cells. Targeted strategies have now been developed that specifically disrupt oncogenically active cell surface receptors and endogenous signaling molecules. These agents have a much greater selectivity for tumor tissue and decreased risk of side effects. Increased signaling through ErbB receptors via gene amplification, overexpression, and mutation has been implicated in many human cancers and associated with poor prognosis. Interruption of this process has been shown to cause antitumor effects. Downregulation of the ErbB receptors, HER-2/neu, and later EGFR, with monoclonal antibodies was the first demonstration of targeted therapy. Subsequently, the ErbB tyrosine kinase domain has been successfully targeted with small molecule inhibitors. The development of novel ErbB-directed entities is ongoing, with particular promise being shown by strategies targeting receptor interaction in oligomeric complexes.
Richter
Mark
M
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Zhang
Hongtao
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases