Novel approaches with targeted therapies in bladder cancer - Therapy of bladder cancer by blockade of the epidermal growth factor receptor family
Novel approaches with targeted therapies in bladder cancer - Therapy of bladder cancer by blockade of the epidermal growth factor receptor family
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DOI：
10.1016/s1040-8428(03)00067-2
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发表时间：
2003-06-27
影响因子：
6.2
通讯作者：
Dinney, CP
中科院分区：
文献类型：
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作者：
Bellmunt, J;Hussain, M;Dinney, CP
对尿路上皮恶性肿瘤分子生物学的进一步了解有助于确定新靶点和预后指标的作用，这些指标可以指导晚期疾病最适当的治疗选择。许多人类肿瘤表达高水平的生长因子及其受体，可用作潜在的治疗靶点。酪氨酸激酶受体，包括许多生长因子受体，如表皮生长因子（EGF）、血管内皮生长因子（VEGF）和Her 2/neu的受体，已发现在尿路上皮肿瘤中过表达。对于这些生长因子受体中的许多，表达程度与癌症的进展和不良预后相关。研究最多的生长因子受体是EGF受体家族的两个成员EGFr（ErbB-1）和Her 2/neu（ErbB-2）。在膀胱癌模型中的几项临床前研究已经证实，全身施用生长因子抑制剂抑制在无胸腺裸鼠膀胱壁中建立的人移行细胞癌的生长和转移。另外的研究表明，EGFR抑制剂的治疗增强了常规细胞减少化疗剂的活性，部分是通过抑制肿瘤细胞增殖、血管生成和诱导细胞凋亡。新的靶向治疗有望改善膀胱癌治疗的当前结果。基于抗HER 2单克隆抗体（Herceptin（R））的成功和EGFR靶向药物（IMC-C225 Cetuximab（R）、ZD 1389 Iressa（R）、OSI-774 Tarceva（R）、GW 57016）在其他肿瘤类型中的有希望的结果，以及基于在临床前模型中获得的结果，人们对在膀胱癌患者中评估这些药物非常感兴趣。目前正在进行几项试验，测试这些新药物单独或与膀胱癌患者化疗联合使用。这些新的生物制剂的整合，可能是补充而不是取代化疗药物，应该是一个主要的研究方向，目的是干扰膀胱癌进展的多个方面。然而，将生物靶向药物整合到膀胱癌患者的综合治疗中的价值仍有待证实。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new targets and prognostic indices that can direct the most appropriate choice of treatment for advanced disease. Many human tumors express high levels of growth factors and their receptors that can be used as potential therapeutical targets. Tyrosine-kinase receptors, including many growth factor receptors such the receptors for epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and Her2/neu, have been found overexpressed in urothelial tumors. For many of these growth factor receptors, the degree of expression has been associated with the progression of cancer and a poor prognosis. Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr (ErbB-1), and Her2/neu (ErbB-2). Several preclinical studies in bladder cancer models, have confirmed that systemic administration of growth factor inhibitors inhibits the growth and metastasis of human transitional cell carcinoma established in the bladder wall of athymic nude mice. Additional studies indicate that therapy with EGFR inhibitors enhances the activity of conventional cytoreductive chemotherapeutic agents, in part by inhibiting tumor cell proliferation, angiogenesis, and inducing apoptosis. Novel targeted therapy hold promise to improve the current results of bladder cancer treatment. Based on the success seen with anti-HER2 monoclonal antibodies (Herceptin(R)) and the promising results with EGFR targeted agents (IMC-C225 Cetuximab(R), ZD 1389 Iressa(R), OSI-774 Tarceva(R), GW 57016) in other tumor types, and based on the results obtained in preclinical models, there is a great interest in assessing these agents in patients with bladder cancer. Several trials are now ongoing testing these new agents alone or in combination with chemotherapy in bladder cancer patients. The integration of these newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression. However, the value of integration of biologically targeted agents into combined modality treatment for patients with bladder cancer has still to be proven. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.