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CRISPR–Cas9 potential for identifying novel therapeutic targets in muscle-invasive bladder cancer
Nature Reviews Urology ( IF 12.1 ) Pub Date : 2024-07-01 , DOI: 10.1038/s41585-024-00901-y
Danielle J. Smith , Sapna Lunj , Antony D. Adamson , Sankari Nagarajan , Tim A. D. Smith , Kimberley J. Reeves , Peter J. Hoskin , Ananya Choudhury

Gene editing technologies help identify the genetic perturbations driving tumour initiation, growth, metastasis and resistance to therapeutics. This wealth of information highlights tumour complexity and is driving cancer research towards precision medicine approaches based on an individual’s tumour genetics. Bladder cancer is the 11th most common cancer in the UK, with high rates of relapse and low survival rates in patients with muscle-invasive bladder cancer (MIBC). MIBC is highly heterogeneous and encompasses multiple molecular subtypes, each with different responses to therapeutics. This evidence highlights the need to identify innovative therapeutic targets to address the challenges posed by this heterogeneity. CRISPR–Cas9 technologies have been used to advance our understanding of MIBC and determine novel drug targets through the identification of drug resistance mechanisms, targetable cell-cycle regulators, and novel tumour suppressor and oncogenes. However, the use of these technologies in the clinic remains a substantial challenge and will require careful consideration of dosage, safety and ethics. CRISPR–Cas9 offers considerable potential for revolutionizing bladder cancer therapies, but substantial research is required for validation before these technologies can be used in the clinical setting.



中文翻译:


CRISPR-Cas9 识别肌肉浸润性膀胱癌新治疗靶点的潜力



基因编辑技术有助于识别驱动肿瘤发生、生长、转移和治疗耐药的基因扰动。这些丰富的信息凸显了肿瘤的复杂性,并正在推动癌症研究朝着基于个体肿瘤遗传学的精准医学方法发展。膀胱癌是英国第 11 位最常见的癌症,肌层浸润性膀胱癌 (MIBC) 患者的复发率高,生存率低。 MIBC 具有高度异质性,包含多种分子亚型,每种亚型对治疗的反应不同。这一证据强调需要确定创新的治疗靶点来应对这种异质性带来的挑战。 CRISPR-Cas9 技术已被用于增进我们对 MIBC 的理解,并通过识别耐药机制、可靶向的细胞周期调节因子以及新型肿瘤抑制基因和癌基因来确定新的药物靶点。然而,这些技术在临床上的使用仍然是一个巨大的挑战,需要仔细考虑剂量、安全性和伦理学。 CRISPR-Cas9 为彻底改变膀胱癌治疗提供了巨大的潜力,但在这些技术应用于临床之前还需要大量研究进行验证。

更新日期:2024-07-02
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