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天然产物在眼部肿瘤致癌转录因子治疗中的靶向作用。

Therapeutic targeting of oncogenic transcription factors by natural products in eye cancer.

机构信息

Dr Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Dr Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

出版信息

Pharmacol Res. 2018 Mar;129:365-374. doi: 10.1016/j.phrs.2017.11.033. Epub 2017 Dec 2.

Abstract

Carcinogenesis has a multifactorial etiology, and the underlying molecular pathogenesis is still not entirely understood, especially for eye cancers. Primary malignant intraocular neoplasms are relatively rare, but delayed detection and inappropriate management contribute to poor outcomes. Conventional treatment, such as orbital exenteration, chemotherapy, or radiotherapy, alone results in high mortality for many of these malignancies. Recent sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve management. Transcription factors are proteins that regulate gene expression by modulating the synthesis of mRNA. Since transcription is a dominant control point in the production of many proteins, transcription factors represent key regulators for numerous cellular functions, including proliferation, differentiation, and apoptosis, making them compelling targets for drug development. Natural compounds have been studied for their potential to be potent yet safe chemotherapeutic drugs. Since the ancient times, plant-derived bioactive molecules have been used to treat dreadful diseases like cancer, and several refined pharmaceutics have been developed from these compounds. Understanding targeting mechanisms of oncogenic transcription factors by natural products can add to our oncologic management toolbox. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in various types of eye cancer.

摘要

致癌作用具有多因素病因,其潜在的分子发病机制尚不完全清楚,特别是对于眼部癌症。原发性眼内恶性肿瘤相对罕见,但由于检测延迟和处理不当,导致预后较差。对于这些恶性肿瘤中的许多肿瘤,单独使用常规治疗方法(如眼眶内容剜除术、化疗或放疗)会导致高死亡率。最近采用高剂量化疗序贯多模式治疗,然后进行适当的手术、放疗和其他辅助化疗,显著改善了治疗效果。转录因子是通过调节 mRNA 的合成来调节基因表达的蛋白质。由于转录是许多蛋白质产生的主要控制点,转录因子是许多细胞功能(包括增殖、分化和凋亡)的关键调节剂,使其成为药物开发的有吸引力的靶点。天然化合物因其具有成为有效且安全的化疗药物的潜力而受到研究。自古以来,植物来源的生物活性分子就被用于治疗癌症等可怕的疾病,并且已经从这些化合物中开发出了几种精制药物。了解天然产物对致癌转录因子的靶向作用机制可以为我们的肿瘤治疗工具箱增加新的内容。本文综述了天然产物在靶向各种眼部癌症中特定致癌转录因子方面的最新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98c6/6176484/b7a0c31444d6/nihms-989939-f0001.jpg

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