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用于乳腺癌的病毒基因治疗:进展与挑战

Viral gene therapy for breast cancer: progress and challenges.

作者信息

Asad Antonela S, Moreno Ayala Mariela A, Gottardo M Florencia, Zuccato Camila, Nicola Candia Alejandro Javier, Zanetti Flavia A, Seilicovich Adriana, Candolfi Marianela

机构信息

a Departamento de Biología Celular e Histología, Facultad de Medicina , Universidad de Buenos Aires , Buenos Aires , Argentina.

b Instituto de Investigaciones Biomédicas (INBIOMED-CONICET/UBA), Facultad de Medicina , Universidad de Buenos Aires , Buenos Aires , Argentina.

出版信息

Expert Opin Biol Ther. 2017 Aug;17(8):945-959. doi: 10.1080/14712598.2017.1338684. Epub 2017 Jun 12.

Abstract

Breast cancer is the most common cancer in women all over the world. Furthermore, up to one third of breast tumors develop metastases that are resistant to standard therapies. Gene therapeutic strategies have been developed in order to specifically target cancer cells either directly or through the stimulation of antitumor immunity. Areas covered: This review describes the therapeutic strategies that are currently under development to treat this disease using engineered viral vectors including: adenovirus, adeno-associated virus, lentivirus, poxvirus, reovirus, baculovirus, herpesvirus and oncolytic viruses. Advantages and disadvantages of these multiple gene therapy platforms are discussed in detail. Expert opinion: Metastatic breast cancer is a perfect candidate for gene therapy approaches due to the presence of several tumor antigens and the aberrant expression of many molecular pathways. Oncolytic vectors are able to attack tumor cells while sparing normal cells and their activity is often enhanced by the administration of chemotherapy. However, more efforts are needed in order to reduce toxicity and to achieve better transduction efficiency. Improved preclinical models and a more critical patient selection for clinical trials, along with advances in gene therapy regulations, will surely facilitate the evolution of gene therapy for the treatment of metastatic breast cancer.

摘要

乳腺癌是全球女性中最常见的癌症。此外,高达三分之一的乳腺肿瘤会发生对标准疗法耐药的转移。已经开发了基因治疗策略,以直接或通过刺激抗肿瘤免疫来特异性靶向癌细胞。涵盖领域:本综述描述了目前正在开发的使用工程化病毒载体治疗该疾病的治疗策略,包括:腺病毒、腺相关病毒、慢病毒、痘病毒、呼肠孤病毒、杆状病毒、疱疹病毒和溶瘤病毒。详细讨论了这些多种基因治疗平台的优缺点。专家观点:转移性乳腺癌由于存在多种肿瘤抗原以及许多分子途径的异常表达,是基因治疗方法的理想候选者。溶瘤载体能够攻击肿瘤细胞,同时不损伤正常细胞,并且其活性通常通过化疗给药而增强。然而,为了降低毒性并实现更好的转导效率,还需要做出更多努力。改进的临床前模型、更严格的临床试验患者选择,以及基因治疗法规的进展,必将促进转移性乳腺癌基因治疗的发展。

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