摘要
肾细胞癌是泌尿系统最致命的恶性肿瘤之一。部分或根治性肾细胞癌切除术是局限性肾细胞癌的主要手术治疗方法,然而,近30%的患者术后会出现复发和转移。转移性肾细胞癌(mRCC)是一种预后非常差的疾病,mRCC的5年生存率通常低于10%。不幸的是,mRCC对化疗和放疗高度耐药。因此,mRCC治疗对研究者和临床医生都是一个巨大的挑战。RCC具有明确的遗传背景,特别是70%以上的病例出现von Hippel-Lindau (VHL)基因丢失或突变。目前已经发现一些影响RCC进展的分子因子和信号通路,包括VHL-HIF-VEGF血管生成信号通路、PI3K/AKT/mTOR信号通路、上皮-间充质转化相关通路、Wnt/β-catenin通路,这些通路在RCC的生长、侵袭性、肾细胞癌的转移和血管生成。基于最近对这些信号通路的研究,一些药物和免疫检查点抑制剂已经被开发出来,对mRCC有潜在的治疗作用。因此,我们的综述旨在总结mRCC治疗的最新进展,特别关注提高mRCC患者药物响应性的策略。
关键词: 肾细胞癌、转移、靶向治疗、耐药、免疫治疗、生物标志物。
Current Medicinal Chemistry
Title:Predictive Biomarkers and Novel Targets in the Treatment of Metastatic Renal Cell Carcinoma
Volume: 28 Issue: 25
关键词: 肾细胞癌、转移、靶向治疗、耐药、免疫治疗、生物标志物。
摘要: Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies. Partial or radical nephrectomy is the major surgical management for localized RCC, however, almost 30% of patients will develop recurrence and metastasis after surgery. Metastatic RCC (mRCC) is a disease with a very poor prognosis, and the 5-year survival of the mRCC is commonly less than 10%. Unfortunately, mRCC is highly resistant to chemo and radiotherapy. Therefore, mRCC treatment has become a big challenge for researchers as well as clinicians. RCC is characterized as clear genetic background, especially with von Hippel-Lindau (VHL) gene loss or mutation in more than 70% of the cases. Several molecular factors and signaling pathways have been discovered to possess impact on the progression of RCC, including VHL-HIF-VEGF angiogenesis signaling, PI3K/AKT/mTOR signaling, epithelial-to-mesenchymal transition-related pathways, and Wnt/β-catenin pathway, which play crucial roles in the growth, invasiveness, metastasis and angiogenesis of RCC. Based on the recent studies of these signaling pathways, some medicines as well as immune check-point inhibitors have been developed, which have shown potential therapeutic effects for mRCC. Therefore, our current review aims to summarize the recent progress of the treatment for mRCC, with a special focus on the strategies to improve the responsiveness of medicines in patients with mRCC.
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Predictive Biomarkers and Novel Targets in the Treatment of Metastatic Renal Cell Carcinoma, Current Medicinal Chemistry 2021; 28 (25) . https://dx.doi.org/10.2174/0929867328666201223124813
DOI https://dx.doi.org/10.2174/0929867328666201223124813 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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