The EGF receptor system as a target for antitumor therapy.
Monoclonal anti-EGF receptor antibodies, EGF receptor antibodies coupled to toxins, TGF alpha-toxin conjugates and tyrosine kinase inhibitors show great potential as antitumor agents. These compounds are effective inhibitors of the EGF receptor system as it functions in the mitogenic stimulation of malignant cells. The effectiveness of cell growth inhibition mediated by anti-EGF receptor antibody and tyrosine kinase inhibitors may prove to be limited and selective. This is in view of the possibility that malignant cell proliferation may be controlled by various mechanisms instead of that which involves the EGF receptor system, despite the expression of both EGF receptor and TGF alpha in the same cell. Other growth control mechanisms could involve hormone receptor systems such as estradiol and the estrogen receptor, oncogene activation or other growth factor-receptor systems. In those malignancies in which growth control resides in the EGF-receptor system, antitumor therapy using monoclonal anti-EGF receptor antibodies and tyrosine kinase inhibitors is a possibility worth pursuing. The effectiveness of immunotoxins and TGF alpha-toxin conjugates may only require the presence of EGF receptor and not be limited to those cells whose growth is controlled exclusively by the EGF receptor system. Nonspecific toxicity may, however, limit the use of these compounds. Further studies assessing the extent of such a toxicity are in order. In the face of the preceding reservations, however, one must not overlook the potential for great achievement as this novel therapeutic avenue is traversed.
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennesse 37232.
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Ennis
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ME
Lippman
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Dickson
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016211:Transforming Growth Factor alpha / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases