双歧杆菌在肿瘤靶向性基因治疗中的应用

The application prospects of probiotic Bifidobacterium in the tumor targeted therapy

肿瘤治疗除传统的手术治疗和放化学治疗外,新兴的抗体或小分子药物靶向治疗因具有特异性抗肿瘤作用和不良反应小等特点,正逐渐成为肿瘤治疗的热点;然而,由于肿瘤细胞的异质性和肿瘤干细胞的存在,特异地针对肿瘤细胞自身进行靶向治疗的难度增加,而且这种靶向治疗只适宜于具有特定标志物的肿瘤患者。实体瘤内存在的乏氧区是肿瘤抵抗治疗的主要原因。双歧杆菌可靶向性定植繁殖于此乏氧区。由于肿瘤的乏氧区不存在肿瘤特异性,因此以双歧杆菌为载体的肿瘤分子靶向治疗方案,可以有效克服传统化学治疗的不良反应和抗体或小分子药物分子靶向治疗的缺陷,使实体瘤内存在的乏氧区不再成为肿瘤治疗的禁区。目前,以双歧杆菌为载体的肿瘤分子靶向治疗已逐渐成为肿瘤靶向治疗的研究热点。本文就肿瘤的细菌疗法,双歧杆菌作为肿瘤靶向治疗载体的基础,双歧杆菌作为靶向治疗载体介导的化学治疗与传统的化学治疗比较,双歧杆菌作为靶向治疗载体与现有肿瘤治疗的其他载体比较,双歧杆菌作为靶向治疗载体的困难与挑战等研究进展作一综述。

Surgery, chemotherapy and radiotherapy are the conventional cancer treatments. Molecular targeted therapy is taken as a promising cancer treatment strategy owing to molecular targeted drugs, such as small molecular compounds or monoclonal antibodies drugs, with higher efficacy and fewer adverse effects compared with conventional treatments. However, many tumors are very heterogeneous and contain cancer stem cells, which increase the risk of cancer targeted therapy, leading to a lower efficacy cancer treatment. Based on the facts： Hypoxic environment exists in the center of solid tumors, which has previously regarded as a source of resistance to chemotherapy and radiotherapy. Hypoxic area is a common feature in all types of tumors and facilitates anaerobic bacteria to localize in this zone. These provide the rationale for targeted therapy by using a probiotic anaerobic bacterium including Bifidobacterium. Probiotic Bifidobacterium can locate and growth in the hypoxic area of solid tumors. Therefore, genetic modified Bifibacterium containing target genes would be used as a very useful tool for cancer treatment, which could make the hypoxic area not be ＂a forbidden area＂. In this review, we will discuss the reason that hypoxic area forms in the solid tumor, the way to use Bifidobacterium as cancer treatment tool, and its related issues including the biosafety, targeted localization, potential application and challenges of genetic modified Bifidobacterium.