Targeted therapies in bladder cancer - an update
Targeted therapies in bladder cancer - an update
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DOI：
10.1016/j.urolonc.2007.05.011
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Dinney, Colin P. N.
中科院分区：
文献类型：
--
作者：
Black, Peter C.;Agarwal, Piyush K.;Dinney, Colin P. N.
膀胱内免疫和化疗，手术和全身化疗都是我们管理膀胱癌患者的关键因素。尽管我们在这些模式方面取得了进展，但我们仍在继续寻求更新的治疗模式以改善患者的预后。针对特定分子通路的新型药物的靶向治疗是实现这种进展的有希望的途径。这份手稿是基于2006年5月泌尿肿瘤学会春季会议上的一次演讲。在这里，我们专注于靶向生长因子及其受体在膀胱癌。特别是，我们总结了我们自己和他人正在进行的基础科学，转化和临床研究在这一领域。在这一系列研究中，最重要的是表皮生长因子受体（EGFR）靶向治疗的小分子抑制剂和单克隆抗体。我们讨论了EGFR导向治疗膀胱癌的基本原理。临床疗效令人失望，已经做了大量的工作来表征用于预测反应的分子标志物。我们自己的一些临床前研究结果有关的血小板衍生生长因子-β（PDGFR-β）和一些背景正在进行的临床试验靶向人表皮生长因子受体2（HER 2）进行了总结。成纤维细胞生长因子3（FGFR 3）有望成为治疗浅表性和侵袭性疾病的潜在靶点。现对FGFR 3突变在膀胱癌中的作用进行综述。最后，我们讨论了VEGF的靶向。最终，可能是使用多激酶抑制剂或将不同抑制剂组合用于产生最佳结果的各种靶点。爱思唯尔公司出版
Intravesical immuno- and chemotherapy, surgery, and systemic chemotherapy are all critical elements in our management of patients with bladder cancer. Despite our advances with these modalities, we continue to seek newer treatment paradigms to improve patient outcome. Targeted therapy with novel agents directed at specific molecular pathways is a promising avenue to achieve such progress. This manuscript is based on a talk given at the Spring Session of the Society of Urologic Oncology in May 2006. Here, we focus on targeting growth factors and their receptors in bladder cancer. In particular, we summarize our own and others' ongoing basic science, translational, and clinical research in this field. Foremost in this line of study is the epidermal growth factor receptor (EGFR)-targeted therapy with small molecule inhibitors and monoclonal antibodies. We discuss the rationale for EGFR-directed therapy in bladder cancer. The clinical efficacy has been disappointing, and extensive work has been done to characterize molecular markers for predicting response. Some of our own preclinical findings related to platelet derived growth factor-beta (PDGFR-beta) and some background on ongoing clinical trials targeting human EGF receptor 2 (HER2) are summarized. Fibroblast growth factor 3 (FGFR3) offers promise as a potential target for therapy of both superficial and invasive disease. The role of FGFR3 mutations in bladder cancer is reviewed. Finally, we discuss the targeting of VEGF. Ultimately, it may be the use of multi-kinase inhibitors or the combination of different inhibitors to various targets that yields the best results. Published by Elsevier Inc.