Black Peter C, Agarwal Piyush K, Dinney Colin P N
Department of Urology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Urol Oncol. 2007 Sep-Oct;25(5):433-8. doi: 10.1016/j.urolonc.2007.05.011.
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.
膀胱内免疫治疗、化疗、手术以及全身化疗都是我们治疗膀胱癌患者的关键要素。尽管我们在这些治疗方式上取得了进展，但我们仍在不断寻求更新的治疗模式以改善患者预后。针对特定分子途径的新型药物靶向治疗是实现这一进展的一条有前景的途径。本手稿基于2006年5月在泌尿肿瘤学会春季会议上的一次演讲。在此，我们聚焦于膀胱癌中生长因子及其受体的靶向治疗。特别地，我们总结了我们自己以及其他人在该领域正在进行的基础科学、转化医学和临床研究。在这一研究领域中，最重要的是用小分子抑制剂和单克隆抗体进行的表皮生长因子受体（EGFR）靶向治疗。我们讨论了EGFR导向治疗膀胱癌的理论依据。其临床疗效令人失望，并且已经开展了大量工作来鉴定预测反应的分子标志物。我们总结了一些与血小板衍生生长因子-β（PDGFR-β）相关的临床前研究结果以及一些针对人表皮生长因子受体2（HER2）的正在进行的临床试验的背景情况。成纤维细胞生长因子3（FGFR3）有望成为浅表性和浸润性疾病治疗的潜在靶点。本文综述了FGFR3突变在膀胱癌中的作用。最后，我们讨论了血管内皮生长因子（VEGF）的靶向治疗。最终，可能是使用多激酶抑制剂或不同抑制剂针对不同靶点的联合应用才能产生最佳效果。
