Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University.
Neurol Med Chir (Tokyo). 2020 Nov 15;60(11):531-542. doi: 10.2176/nmc.ra.2020-0175. Epub 2020 Oct 16.
As a result of rapid progress in genome medicine technologies, such as the evolution of DNA sequencing and the development of molecular targeted drugs, the era of precision cancer medicine has begun. In 2019, a nationwide genome medicine system was established and cancer gene panel sequencing began being covered by national health insurance in Japan. However, patients with brain tumors have not benefited much from genome medicine, even though gliomas contain many potential molecular targets, such as alterations in EGFR, IDH1/2, BRAF, and Histone H3K27. Targeted therapies for these molecules are currently under enthusiastic development; however, such attempts have not yet achieved remarkable success. To date, only a limited number of targeted drugs for brain tumors such as immune checkpoint, neurotrophic tyrosine receptor kinase (NTRK), and Bruton tyrosine kinase (BTK) inhibitors are available, and only in limited cases. Several obstacles remain in the development of drugs to treat brain tumors, including the difficulties in conducting clinical trials because of the relatively rare incidence and in drug delivery through the blood-brain barrier (BBB). Furthermore, general problems for numerous types of cancer, such as tumor heterogeneity, also exist for brain tumors. We hope that overcoming these issues could enable precision genome medicine to be more beneficial for patients with brain tumors such as malignant gliomas. In addition, careful consideration of ethical, legal, and social issues (ELSIs) is important as it is indispensable for maintaining good relationships with patients, which is one of the keys for genome medicine promotion.
由于基因组医学技术的快速进步,例如 DNA 测序的发展和分子靶向药物的开发,精准癌症医学的时代已经开始。2019 年,日本建立了全国性的基因组医学系统,癌症基因panel 测序开始被纳入国家医疗保险。然而,脑肿瘤患者并没有从基因组医学中获益太多,尽管神经胶质瘤包含许多潜在的分子靶点,如 EGFR、IDH1/2、BRAF 和组蛋白 H3K27 的改变。目前正在积极开发针对这些分子的靶向治疗方法;然而,这些尝试尚未取得显著成功。迄今为止,脑肿瘤的靶向药物(如免疫检查点抑制剂、神经营养酪氨酸受体激酶(NTRK)抑制剂和 Bruton 酪氨酸激酶(BTK)抑制剂)数量有限,且仅在有限的情况下可用。在开发治疗脑肿瘤的药物方面仍存在几个障碍,包括由于发病率相对较低,临床试验难以进行,以及药物难以通过血脑屏障(BBB)进行输送。此外,脑肿瘤还存在与其他多种癌症共同的一般性问题,如肿瘤异质性。我们希望克服这些问题能够使精准基因组医学对恶性神经胶质瘤等脑肿瘤患者更有益。此外,仔细考虑伦理、法律和社会问题(ELSI)非常重要,因为这对于与患者保持良好关系是不可或缺的,这是基因组医学推广的关键之一。