摘要
手术切除是胃肠癌患者的唯一治疗选择。不幸的是,大部分患者被诊断已为晚期,此时进行手术是不可能的。而某些类型的肿瘤如肝细胞癌和胰腺癌等发病率和死亡率在全球范围内稳步增加。尽管分子靶向治疗癌症在发展,但是对病人的存活率的影响已经相当有限。单药治疗不太可能会最终成功。越来越多的研究领域集中在传统化疗(如环磷酰胺、吉西他滨、紫杉醇和阿霉素)与放疗和/或基因治疗结合的策略。联合的方法似乎是必要的,因为多个肿瘤的耐药机制限制化疗药物的效果(如多药耐药性的发生或表观遗传变化)、逃避免疫反应(如诱导调节性T细胞或myeloid-derived抑制细胞)和产生抵抗抗血管生成或放射治疗。例如低氧诱导因子的感应。此外,新的研究表明低剂量的常规化疗和基因疗法可以产生协同作用机制,能够实现针对不同类型肿瘤的治疗效果。尽管癌症基因治疗还没有在临床实践,但是其治疗效果最近被看好,尤其是标准化疗或放射治疗的结合应用。
关键词: 胃肠的,癌症,基因治疗,联合治疗策略,放射疗法,免疫疗法
Current Gene Therapy
Title:Combined Therapy for Gastrointestinal Carcinomas: Exploiting Synergies Between Gene Therapy and Classical Chemo-Radiotherapy
Volume: 15 Issue: 2
Author(s): Mariana Malvicini, Jorge B. Aquino and Guillermo Mazzolini
Affiliation:
关键词: 胃肠的,癌症,基因治疗,联合治疗策略,放射疗法,免疫疗法
摘要: Surgical resection is the only curative option for patients with gastrointestinal carcinomas. Unfortunately, the majority of patients are diagnosed in advanced stages when surgery is not possible. Moreover, the incidence and mortality for certain type of tumors such as hepatocellular carcinoma or pancreatic cancer are steadily increasing worldwide. In spite of the advances in the development of molecular targeted therapies for cancer, the impact on patient survival has been rather limited. It is unlikely that individual agents would be ultimately successful as monotherapy. There is a growing area of research focused on the combination of classical chemotherapy (e.g. cyclophosphamide, gemcitabine, paclitaxel and doxorubicin) with radiotherapy and/or gene therapy strategies. Combined approaches seem to be required due to multiple resistance mechanisms that tumors utilize to limit the activity of chemotherapeutic agents (e.g. the occurrence of multidrug resistance or epigenetic alterations), evade immune responses (e.g. induction of regulatory T cells or myeloid-derived suppressor cells) and to generate resistance against anti-angiogenesis or to radiotherapy by, for example, the induction of hypoxia-inducible factor 1. In addition, new studies suggest that combination of low dose of conventional chemotherapy and gene therapy could allow the development of synergic mechanisms able to achieve significant therapeutic effects against diverse tumors. Although cancer gene therapy is not yet available in clinical practice, advances being recently made look promising, especially when it was applied in combination with standard chemo- or radiotherapy protocols.
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Mariana Malvicini, Jorge B. Aquino and Guillermo Mazzolini , Combined Therapy for Gastrointestinal Carcinomas: Exploiting Synergies Between Gene Therapy and Classical Chemo-Radiotherapy, Current Gene Therapy 2015; 15 (2) . https://dx.doi.org/10.2174/1566523214666141224095757
DOI https://dx.doi.org/10.2174/1566523214666141224095757 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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