Ennis B W, Lippman M E, Dickson R B
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennesse 37232.
Cancer Invest. 1991;9(5):553-62. doi: 10.3109/07357909109018953.
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.
单克隆抗表皮生长因子（EGF）受体抗体、与毒素偶联的EGF受体抗体、转化生长因子α（TGFα）-毒素偶联物以及酪氨酸激酶抑制剂作为抗肿瘤药物显示出巨大潜力。这些化合物是EGF受体系统的有效抑制剂，该系统在恶性细胞的有丝分裂刺激中发挥作用。由抗EGF受体抗体和酪氨酸激酶抑制剂介导的细胞生长抑制的有效性可能被证明是有限的且具有选择性。鉴于尽管同一细胞中同时表达EGF受体和TGFα，但恶性细胞增殖可能由多种机制控制，而非涉及EGF受体系统的机制。其他生长控制机制可能涉及激素受体系统，如雌二醇和雌激素受体、癌基因激活或其他生长因子-受体系统。在那些生长控制依赖于EGF受体系统的恶性肿瘤中，使用单克隆抗EGF受体抗体和酪氨酸激酶抑制剂进行抗肿瘤治疗是值得探索的可能性。免疫毒素和TGFα-毒素偶联物的有效性可能仅需要EGF受体的存在，而不限于那些生长仅由EGF受体系统控制的细胞。然而，非特异性毒性可能会限制这些化合物的使用。进一步评估这种毒性程度的研究势在必行。然而，尽管有上述保留意见，但在探索这条新的治疗途径时，绝不能忽视取得巨大成就的潜力。
