肿瘤基因治疗研究进展

Ganesh G. Dhakad, Sangita P. Shirsat, Kaveri P. Tmabe, N. Jaiswal
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引用次数: 0

摘要

临床试验中基于基因的癌症治疗包括免疫治疗和化疗方法的增强策略。这些策略包括体外和体内细胞因子基因转移、药物前递送基因致敏以及使用耐药基因保护骨髓免受大剂量化疗的影响。癌基因表达的失活和肿瘤抑制基因的基因替代是靶向癌细胞中潜在遗传病变的策略之一。对迄今为止的临床试验结果的回顾,主要是在对常规治疗难治的晚期癌症患者中,表明这些治疗可以以可接受的低毒性介导肿瘤消退。媒介发展仍然是未来研究的关键领域。未来研究的重要领域包括修饰病毒载体以降低毒性和免疫原性,提高非病毒载体的转导效率,增强载体的靶向性和特异性,调节基因表达,以及确定基于基因的药物与其他癌症治疗方法之间的协同作用。
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Review on Gene Therapy on Cancer
Gene-based therapies for cancer in clinical trials include strategies that involve augmentation of immunotherapeutic and chemotherapeutic approaches. These strategies include ex vivo and in vivo cytokine gene transfer, drug sensitization with genes for prodrug delivery, and the use of drug-resistance genes for bone marrow protection from high-dose chemotherapy. Inactivation of oncogene expression and gene replacement for tumor suppressor genes are among the strategies for targeting the underlying genetic lesions in the cancer cell. A review of clinical trial results to date, primarily in patients with very advanced cancers refractory to conventional treatments, indicates that these treatments can mediate tumor regression with acceptably low toxicity. Vector development remains a critical area for future research. Important areas for future research include modifying viral vectors to reduce toxicity and immunogenicity, increasing the transduction efficiency of nonviral vectors, enhancing vector targeting and specificity, regulating gene expression, and identifying synergies between gene-based agents and other cancer therapeutics.
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