PDF(Pubmed)
Abstract：
OBJECTIVE: Neurofibromatosis type 1 (NF-1) is a cancer predisposition syndrome caused by mutations in the NF1 tumor suppressor gene that encodes the neurofibromin protein, which functions as a negative regulator of Ras signaling. We review the past, current, and future state of therapeutic strategies for tumors associated with NF-1.
RESULTS: Therapeutic efforts for NF-1-associated tumors have centered around inhibiting Ras output, leading to the clinical success of downstream MEK inhibition for plexiform neurofibromas and low-grade gliomas. However, MEK inhibition and similar molecular monotherapy approaches that block Ras signaling do not work for all patients and show limited efficacy for more aggressive cancers such as malignant peripheral nerve sheath tumors and high-grade gliomas, motivating novel treatment approaches. We highlight the current therapeutic landscape for NF-1-associated tumors, broadly categorizing treatment into past strategies for serial Ras pathway blockade, current approaches targeting parallel oncogenic and tumor suppressor pathways, and future avenues of investigation leveraging biologic and technical innovations in immunotherapy, pharmacology, and gene delivery.
RESULTS: Therapeutic efforts for NF-1-associated tumors have centered around inhibiting Ras output, leading to the clinical success of downstream MEK inhibition for plexiform neurofibromas and low-grade gliomas. However, MEK inhibition and similar molecular monotherapy approaches that block Ras signaling do not work for all patients and show limited efficacy for more aggressive cancers such as malignant peripheral nerve sheath tumors and high-grade gliomas, motivating novel treatment approaches. We highlight the current therapeutic landscape for NF-1-associated tumors, broadly categorizing treatment into past strategies for serial Ras pathway blockade, current approaches targeting parallel oncogenic and tumor suppressor pathways, and future avenues of investigation leveraging biologic and technical innovations in immunotherapy, pharmacology, and gene delivery.
摘要：
目的：1型神经纤维瘤病（NF-1）是由编码神经纤维蛋白的NF1肿瘤抑制基因突变引起的癌症易感性综合征，它充当Ras信号的负调节剂。我们回顾过去，电流,以及与NF-1相关的肿瘤的治疗策略的未来状态。
结果：NF-1相关肿瘤的治疗努力集中在抑制Ras输出，导致下游MEK抑制丛状神经纤维瘤和低度胶质瘤的临床成功。然而,MEK抑制和阻断Ras信号的类似分子单一疗法方法并不适用于所有患者，并且对更具侵袭性的癌症（如恶性外周神经鞘瘤和高级别神经胶质瘤）显示有限的疗效。激发新的治疗方法。我们强调目前NF-1相关肿瘤的治疗前景，将治疗广泛分类为过去的Ras途径阻断策略，目前的方法针对平行的致癌和肿瘤抑制途径，以及利用免疫疗法中的生物和技术创新的未来研究途径，药理学,和基因传递。
结果：NF-1相关肿瘤的治疗努力集中在抑制Ras输出，导致下游MEK抑制丛状神经纤维瘤和低度胶质瘤的临床成功。然而,MEK抑制和阻断Ras信号的类似分子单一疗法方法并不适用于所有患者，并且对更具侵袭性的癌症（如恶性外周神经鞘瘤和高级别神经胶质瘤）显示有限的疗效。激发新的治疗方法。我们强调目前NF-1相关肿瘤的治疗前景，将治疗广泛分类为过去的Ras途径阻断策略，目前的方法针对平行的致癌和肿瘤抑制途径，以及利用免疫疗法中的生物和技术创新的未来研究途径，药理学,和基因传递。
