Zumkeller W, Schofield P N
Department of Paediatric Oncology and Haematology, University Hospital Eppendorf, Hamburg, Germany.
Anticancer Res. 1995 Mar-Apr;15(2):343-8.
A wide range of growth factors has been identified in recent years, some of which have been found to play a crucial role in neoplastic processes. Some tumours produce considerable amounts of these peptides and their requirement for growth factors is often much reduced leading to a degree of autonomy which may itself contribute to tumourigenicity. In addition, growth factors such as TGF-alpha, PDGF, FGF and IGFs have been found to be overexpressed in tumours. The growth factor effector pathway is thus open to intervention, e.g. by blocking the receptor using specific antibodies or interfering with posttranscriptional activation. This is even more evident as oncogenes such as erbB and v-sis encode for growth factor receptors. Soluble receptors, due to high affinity binding, might also be used to sequester growth factors from its specific membrane-bound receptors. Tyrosine-specific protein kinase activity may be inhibited by tyrosine analogues such as erbstatin or by more specific tyrosine-kinase inhibitors. Some therapeutical concepts have already been developed in clinical trials. Tumour necrosis factor (TNF) has successfully been used in extremity melanoma and sarcoma and monoclonal antibodies directed against the EGF receptor has also been applied in patients with advanced squamous lung cancer. Synthetic growth factor analogues which bind to the receptor without eliciting a signal may soon become a supplementary part in cancer treatment. Growth factor action is also blocked by suramin and its analogues and clinical phase I and II trials are underway. These novel therapeutical aspects will profoundly change the nature of cancer treatment.
近年来已鉴定出多种生长因子，其中一些已被发现在肿瘤形成过程中起关键作用。一些肿瘤会产生大量此类肽，并且它们对生长因子的需求通常会大大降低，从而导致一定程度的自主性，这本身可能有助于肿瘤发生。此外，已发现诸如转化生长因子-α（TGF-α）、血小板衍生生长因子（PDGF）、成纤维细胞生长因子（FGF）和胰岛素样生长因子（IGF）等生长因子在肿瘤中过度表达。因此，生长因子效应途径易于干预，例如通过使用特异性抗体阻断受体或干扰转录后激活。这一点在诸如erbB和v-sis等癌基因编码生长因子受体时更为明显。由于具有高亲和力结合，可溶性受体也可用于从其特异性膜结合受体中隔离生长因子。酪氨酸特异性蛋白激酶活性可被诸如埃博霉素等酪氨酸类似物或更特异性的酪氨酸激酶抑制剂抑制。一些治疗概念已在临床试验中得到发展。肿瘤坏死因子（TNF）已成功用于四肢黑色素瘤和肉瘤，针对表皮生长因子（EGF）受体的单克隆抗体也已应用于晚期肺鳞状癌患者。与受体结合而不引发信号的合成生长因子类似物可能很快成为癌症治疗的一个补充部分。苏拉明及其类似物也可阻断生长因子的作用，目前正在进行I期和II期临床试验。这些新的治疗方法将深刻改变癌症治疗的性质。
