Ghiaseddin Ashley, Hoang Minh Lan B, Janiszewska Michalina, Shin David, Wick Wolfgang, Mitchell Duane A, Wen Patrick Y, Grossman Stuart A
Department of Neurosurgery, University of Florida, Gainesville, Florida, USA.
Department of Molecular Medicine, Scripps Research Florida, Jupiter, Florida, USA.
Neurooncol Adv. 2020 Oct 24;3(1):vdaa145. doi: 10.1093/noajnl/vdaa145. eCollection 2021 Jan-Dec.
Despite therapeutic advances for other malignancies, gliomas remain challenging solid tumors to treat. Complete surgical resection is nearly impossible due to gliomas' diffuse infiltrative nature, and treatment is hampered by restricted access to the tumors due to limited transport across the blood-brain barrier. Recent advances in genomic studies and next-generation sequencing techniques have led to a better understanding of gliomas and identification of potential aberrant signaling pathways. Targeting the specific genomic abnormalities via novel molecular therapies has opened a new avenue in the management of gliomas, with encouraging results in preclinical studies and early clinical trials. However, molecular characterization of gliomas revealed significant heterogeneity, which poses a challenge for targeted therapeutic approaches. In this context, leading neuro-oncology researchers and clinicians, industry innovators, and patient advocates convened at the inaugural annual Remission Summit held in Orlando, FL in February 2019 to discuss the latest advances in immunotherapy and precision medicine approaches for the treatment of adult and pediatric brain tumors and outline the unanswered questions, challenges, and opportunities that lay ahead for advancing the duration and quality of life for patients with brain tumors. Here, we provide historical context for precision medicine in other cancers, present emerging approaches for gliomas, discuss their limitations, and outline the steps necessary for future success. We focus on the advances in small molecule targeted therapy, as the use of immunotherapy as an emerging precision medicine modality for glioma treatment has recently been reviewed by our colleagues.
尽管在其他恶性肿瘤的治疗方面取得了进展，但胶质瘤仍然是具有挑战性的实体瘤。由于胶质瘤具有弥漫性浸润的特性，几乎不可能进行完整的手术切除，而且由于血脑屏障限制了药物转运，导致肿瘤难以接近，治疗受到阻碍。基因组研究和新一代测序技术的最新进展使人们对胶质瘤有了更好的理解，并确定了潜在的异常信号通路。通过新型分子疗法靶向特定的基因组异常为胶质瘤的治疗开辟了一条新途径，在临床前研究和早期临床试验中取得了令人鼓舞的结果。然而，胶质瘤的分子特征显示出显著的异质性，这给靶向治疗方法带来了挑战。在此背景下，顶尖的神经肿瘤学研究人员、临床医生、行业创新者以及患者权益倡导者于2019年2月在佛罗里达州奥兰多市举行的首届年度缓解峰会上齐聚一堂，讨论成人和儿童脑肿瘤治疗中免疫疗法和精准医学方法的最新进展，并概述在延长脑肿瘤患者生存期和提高生活质量方面尚未解决的问题、挑战和机遇。在此，我们提供其他癌症精准医学的历史背景，介绍胶质瘤的新兴治疗方法，讨论其局限性，并概述未来取得成功所需的步骤。我们重点关注小分子靶向治疗的进展，因为我们的同事最近已对免疫疗法作为胶质瘤治疗新兴精准医学模式的应用进行了综述。
