Department of Medicine, Stony Brook University Hospital, 9447 SUNY, Stony Brook, NY, 11794-9447, USA.
Division of Hematology/Oncology, Department of Medicine, Northport VA Medical Center, Northport, NY, USA.
J Hematol Oncol. 2019 Sep 4;12(1):89. doi: 10.1186/s13045-019-0780-z.
The treatment of genitourinary malignancies has dramatically evolved over recent years. Renal cell carcinoma, urothelial carcinoma of the bladder, and prostate adenocarcinoma are the most commonly encountered genitourinary malignancies and represent a heterogeneous population of cancers, in both histology and approach to treatment. However, all three cancers have undergone paradigm shifts in their respective therapeutic landscapes due to a greater understanding of their underlying molecular mechanisms and oncogenic drivers. The advance that has gained the most recent traction has been the advent of immunotherapies, particularly immune checkpoint inhibitors. Immunotherapy has increased overall survival and even provided durable responses in the metastatic setting in some patients. The early success of immune checkpoint inhibitors has led to further drug development with the emergence of novel agents which modulate the immune system within the tumor microenvironment. Notwithstanding immunotherapy, investigators are also developing novel agents tailored to a variety of targets including small-molecule tyrosine kinase inhibitors, mTOR inhibitors, and novel fusion proteins to name a few. Erdafitinib has become the first targeted therapy approved for metastatic bladder cancer. Moreover, the combination therapy of immune checkpoint inhibitors with targeted agents such as pembrolizumab or avelumab with axitinib has demonstrated both safety and efficacy and just received FDA approval for their use. We are in an era of rapid progression in drug development with multiple exciting trials and ongoing pre-clinical studies. We highlight many of the promising new emerging therapies that will likely continue to improve outcomes in patients with genitourinary malignancies.
近年来，泌尿生殖系统恶性肿瘤的治疗取得了显著进展。肾细胞癌、膀胱尿路上皮癌和前列腺腺癌是最常见的泌尿生殖系统恶性肿瘤，代表了一组在组织学和治疗方法上具有异质性的癌症。然而，由于对其潜在分子机制和致癌驱动因素有了更深入的了解，这三种癌症在各自的治疗领域都发生了范式转变。最近最受关注的进展是免疫疗法的出现，特别是免疫检查点抑制剂。免疫疗法提高了总体生存率，甚至在某些患者的转移性环境中提供了持久的反应。免疫检查点抑制剂的早期成功促使研究人员开发出更多的药物，这些药物通过调节肿瘤微环境中的免疫系统来发挥作用。尽管有免疫疗法，研究人员也在开发针对各种靶点的新型药物，包括小分子酪氨酸激酶抑制剂、mTOR 抑制剂和新型融合蛋白等。厄达替尼已成为第一种获批用于转移性膀胱癌的靶向治疗药物。此外，免疫检查点抑制剂与靶向药物（如 pembrolizumab 或avelumab 联合 axitinib）的联合治疗已显示出安全性和疗效，并刚刚获得 FDA 批准用于该用途。我们正处于药物开发的快速发展阶段，有许多令人兴奋的试验和正在进行的临床前研究。我们强调了许多有前途的新兴疗法，这些疗法有望继续改善泌尿生殖系统恶性肿瘤患者的预后。
