下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Gene Therapy: Transforming the Battle Against Pancreatic Cancer.
Gene Therapy: Transforming the Battle Against Pancreatic Cancer.
胰腺癌仍然是最具侵袭性和致死性的恶性肿瘤之一,尽管传统治疗方式取得了进展,但其预后仍然极差。
胰腺癌仍然是最具侵袭性和致死性的恶性肿瘤之一,尽管传统治疗方式取得了进展,其预后仍然极差。基因治疗通过靶向潜在的遗传改变并利用免疫系统的力量,已成为对抗胰腺癌的一种有前景的方法。本综述探讨了胰腺癌基因治疗策略的当前格局,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。基因替代治疗旨在恢复抑癌基因如 TP53 的功能,而基因沉默则靶向癌基因如 KRAS(Kirsten 大鼠肉瘤病毒癌基因同源物)以抑制肿瘤生长。免疫治疗增强,特别是通过嵌合抗原受体(CAR)T 细胞治疗,已显示出克服免疫抑制性肿瘤微环境的潜力。溶瘤病毒经过工程改造,能够选择性地在癌细胞中复制并摧毁癌细胞,已在临床前模型中显示出疗效,并正在临床试验中进行评估。近期进展,包括使用新抗原 T 细胞受体基因治疗成功治疗一名晚期胰腺癌患者,凸显了个性化基因治疗方法的潜力。然而,要实现基因治疗对胰腺癌的全部潜力,必须解决精确基因递送、肿瘤异质性和伦理考量等挑战。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铺平道路,为改善胰腺癌的预后带来希望。
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.
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