Thomas Jonathan, Sonpavde Guru
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cancers (Basel). 2022 Apr 1;14(7):1795. doi: 10.3390/cancers14071795.
Despite the introduction of immune checkpoint inhibitors and antibody-drug conjugates to the management of advanced urothelial carcinoma, the disease is generally incurable. The increasing incorporation of next-generation sequencing of tumor tissue into the characterization of bladder cancer has led to a better understanding of the somatic genetic aberrations potentially involved in its pathogenesis. Genetic alterations have been observed in kinases, such as FGFRs, ErbBs, PI3K/Akt/mTOR, and Ras-MAPK, and genetic alterations in critical cellular processes, such as chromatin remodeling, cell cycle regulation, and DNA damage repair. However, activating mutations or fusions of and remains the only validated therapeutically actionable alteration, with erdafitinib as the only targeted agent currently approved for this group. Bladder cancer is characterized by genomic heterogeneity and a high tumor mutation burden. This review highlights the potential relevance of aberrations and discusses the current status of targeted therapies directed at them.
尽管免疫检查点抑制剂和抗体药物偶联物已被用于晚期尿路上皮癌的治疗，但该疾病通常仍无法治愈。将肿瘤组织的下一代测序越来越多地纳入膀胱癌的特征描述中，这使得人们对可能参与其发病机制的体细胞基因畸变有了更好的理解。在激酶中观察到了基因改变，如FGFRs、ErbBs、PI3K/Akt/mTOR和Ras-MAPK，以及在关键细胞过程中的基因改变，如染色质重塑、细胞周期调控和DNA损伤修复。然而， 和 的激活突变或融合仍然是唯一经过验证的可治疗的可操作改变，erdafitinib是目前唯一被批准用于该组的靶向药物。膀胱癌的特点是基因组异质性和高肿瘤突变负荷。本综述强调了畸变的潜在相关性，并讨论了针对这些畸变的靶向治疗的现状。
