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前列腺癌的基因治疗。

Gene therapy for prostate cancer.

机构信息

Cork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.

出版信息

Postgrad Med. 2010 May;122(3):166-80. doi: 10.3810/pgm.2010.05.2154.

Abstract

Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor's vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or in combination with current approaches.

摘要

癌症仍然是发病率和死亡率的主要原因。尽管在理解、检测和治疗方面取得了进展,但它仍占西方国家每年近四分之一的死亡人数。前列腺癌是目前欧洲和美国男性最常见的非皮肤癌,占男性所有癌症的 15%。随着个体预期寿命的增加,预计前列腺癌的发病率和死亡率也将增加。前列腺癌在初始表现时可能无法手术,对化疗和放疗无反应,或在适当治疗后复发。在出现时,患者的组织中可能已经有转移。预防肿瘤复发需要系统治疗;然而,目前的方法受到毒性或疗效不足的限制。对于有这种转移性癌症的患者,开发替代疗法至关重要。基因治疗是治疗前列腺癌和其他癌症的一种现实前景,涉及向患者输送遗传信息,以促进治疗性蛋白质的产生。治疗剂可以直接作用(例如,通过诱导肿瘤细胞产生细胞毒性剂)或间接作用,通过上调免疫系统来有效靶向肿瘤细胞或通过破坏肿瘤的血管系统。然而,在实现高效和安全的基因药物之前,必须解决技术难题(主要是通过开发一种安全有效地将基因递送到靶细胞或组织的方法)。在过去的 20 年中,已经进行了大量的研究,涉及临床前和临床试验水平治疗前列腺癌的各种策略。这些方法中的许多方法在患者中观察到的治疗效果表明,这些治疗方式将作为临床泌尿科恶性肿瘤治疗的重要组成部分,无论是单独使用还是与当前方法联合使用。

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