Moon Chulso, Oh Yun, Roth Jack A
Department of Otolaryngology and Oncology, The Johns Hopkins School of Medicine and The Sidney Kimmel Cancer Center, Baltimore, Maryland 21205, USA.
Clin Cancer Res. 2003 Nov 1;9(14):5055-67.
Targeting the specific genetic lesions responsible for carcinogenesis and cancer progression is an attractive strategy for developing more effective anticancer therapeutics and reducing treatment-related toxicity. The restoration of defective tumor suppressor gene pathways by replacement of tumor suppressor genes in cancer cells has been studied in lung cancer and head and neck cancer (HNC). The most extensively studied agent is the wild-type p53 tumor suppressor gene delivered by an adenoviral vector. Clinical trials to date in non-small cell lung cancer and HNC have consistently shown evidence of gene transduction and expression, mediation of apoptosis, and clinical responses including pathological complete responses. It is also clear, however, that this approach can be improved further. Promising avenues for investigation include improved gene delivery systems, induction of bystander effects, design of immunogene and antiangiogenesis gene therapies, and adjuvant use of gene therapy with conventional chemotherapy, radiation therapy, and surgery. These strategies, however, will need further refinement to succeed clinically. This review examines several important issues in cancer gene therapy in general and the most recent achievements in gene therapy for HNC and non-small cell lung cancer.
针对导致癌症发生和进展的特定基因损伤，是开发更有效抗癌疗法并降低治疗相关毒性的一种有吸引力的策略。通过在癌细胞中替换肿瘤抑制基因来恢复有缺陷的肿瘤抑制基因通路，已在肺癌和头颈癌（HNC）中得到研究。研究最广泛的试剂是由腺病毒载体递送的野生型p53肿瘤抑制基因。迄今为止，在非小细胞肺癌和头颈癌中的临床试验一直显示出基因转导和表达、凋亡介导以及包括病理完全缓解在内的临床反应的证据。然而，同样清楚的是，这种方法可以进一步改进。有前景的研究途径包括改进基因递送系统、诱导旁观者效应、免疫基因和抗血管生成基因疗法的设计，以及基因疗法与传统化疗、放疗和手术的辅助使用。然而，这些策略需要进一步完善才能在临床上取得成功。本综述探讨了癌症基因治疗中的几个重要问题，以及头颈癌和非小细胞肺癌基因治疗的最新成果。
