{"title":"基因疗法:改变对抗胰腺癌的战斗。","authors":"Rohit Sharma, Sourabh Kumar, Rashmi Ghosh, Kumari Komal, Manish Kumar","doi":"10.2174/0115665232364196250131102330","DOIUrl":null,"url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most aggressive and lethal malignancies, with a dismal prognosis despite advancements in conventional treatment modalities. Gene therapy has emerged as a promising approach to combat pancreatic cancer by targeting the underlying genetic alterations and harnessing the power of the immune system. This review explores the current landscape of gene therapy strategies for pancreatic cancer, including gene replacement therapy, gene silencing, immunotherapy enhancement, and oncolytic virotherapy. Gene replacement therapy aims to restore the function of tumor suppressor genes, such as TP53, while gene silencing targets oncogenes like KRAS (Kirsten rat sarcoma viral oncogene homolog) to inhibit tumor growth. Immunotherapy enhancement, particularly through chimeric antigen receptor (CAR) T-cell therapy, has shown potential in overcoming the immunosuppressive tumor microenvironment. Oncolytic viruses, engineered to replicate in and destroy cancer cells selectively, have demonstrated efficacy in preclinical models and are being evaluated in clinical trials. Recent advances, including the successful treatment of a patient with advanced pancreatic cancer using neoantigen T-cell receptor gene therapy, highlight the potential of personalized gene therapy approaches. However, challenges such as precise gene delivery, tumor heterogeneity, and ethical considerations must be addressed to realize the potential of gene therapy for pancreatic cancer fully. 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Recent advances, including the successful treatment of a patient with advanced pancreatic cancer using neoantigen T-cell receptor gene therapy, highlight the potential of personalized gene therapy approaches. However, challenges such as precise gene delivery, tumor heterogeneity, and ethical considerations must be addressed to realize the potential of gene therapy for pancreatic cancer fully. 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引用次数: 0
摘要
胰腺癌仍然是最具侵袭性和致命性的恶性肿瘤之一,尽管传统治疗方式取得了进步,但预后却很差。通过靶向潜在的基因改变和利用免疫系统的力量,基因治疗已经成为对抗胰腺癌的一种很有前途的方法。本文综述了胰腺癌基因治疗策略的现状,包括基因替代治疗、基因沉默、免疫治疗增强和溶瘤病毒治疗。基因替代疗法旨在恢复肿瘤抑制基因(如TP53)的功能,而基因沉默则针对癌基因(如KRAS (Kirsten rat sarcoma viral癌基因同源物))来抑制肿瘤生长。免疫治疗增强,特别是通过嵌合抗原受体(CAR) t细胞治疗,已经显示出克服免疫抑制肿瘤微环境的潜力。溶瘤病毒被设计成选择性地在癌细胞中复制和破坏癌细胞,已在临床前模型中证明了有效性,并正在临床试验中进行评估。最近的进展,包括使用新抗原t细胞受体基因疗法成功治疗晚期胰腺癌患者,突出了个性化基因治疗方法的潜力。然而,为了充分发挥基因治疗胰腺癌的潜力,必须解决诸如精确基因传递、肿瘤异质性和伦理考虑等挑战。正在进行的研究和临床试验有望为开发安全有效的基因疗法提供便利,为改善胰腺癌的预后带来希望。
Gene Therapy: Transforming the Battle Against Pancreatic Cancer.
Pancreatic cancer remains one of the most aggressive and lethal malignancies, with a dismal prognosis despite advancements in conventional treatment modalities. Gene therapy has emerged as a promising approach to combat pancreatic cancer by targeting the underlying genetic alterations and harnessing the power of the immune system. This review explores the current landscape of gene therapy strategies for pancreatic cancer, including gene replacement therapy, gene silencing, immunotherapy enhancement, and oncolytic virotherapy. Gene replacement therapy aims to restore the function of tumor suppressor genes, such as TP53, while gene silencing targets oncogenes like KRAS (Kirsten rat sarcoma viral oncogene homolog) to inhibit tumor growth. Immunotherapy enhancement, particularly through chimeric antigen receptor (CAR) T-cell therapy, has shown potential in overcoming the immunosuppressive tumor microenvironment. Oncolytic viruses, engineered to replicate in and destroy cancer cells selectively, have demonstrated efficacy in preclinical models and are being evaluated in clinical trials. Recent advances, including the successful treatment of a patient with advanced pancreatic cancer using neoantigen T-cell receptor gene therapy, highlight the potential of personalized gene therapy approaches. However, challenges such as precise gene delivery, tumor heterogeneity, and ethical considerations must be addressed to realize the potential of gene therapy for pancreatic cancer fully. Ongoing research and clinical trials are expected to facilitate the way for the development of safe and effective gene therapies, offering hope for improved outcomes in pancreatic cancer.
期刊介绍:
Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases.
Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.