HDAC 和 PI3K 拮抗剂协同抑制 MYC 驱动的髓母细胞瘤生长。
HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma.
机构信息
Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Cancer and Immunology Department, Brain Tumor Institute, Children's National Medical Center, Washington, DC 20010, USA.
Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
出版信息
Cancer Cell. 2016 Mar 14;29(3):311-323. doi: 10.1016/j.ccell.2016.02.011.
Abstract
Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACIs). HDACIs potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the FOXO1 tumor suppressor gene. HDACIs also synergize with phosphatidylinositol 3-kinase inhibitors to inhibit tumor growth in vivo. These studies identify an effective combination therapy for the most aggressive form of MB.
摘要
髓母细胞瘤（MB）是一种高度恶性的小儿脑肿瘤。尽管采用了积极的治疗方法，但许多患者仍死于该疾病，而幸存者则会因治疗而产生严重的副作用。由 MYC 驱动的 MB 预后特别差，非常需要更有效的治疗方法。我们使用 MYC 驱动的 MB 动物模型筛选出能降低肿瘤细胞活力的药物。最有效的化合物之一是组蛋白去乙酰化酶抑制剂（HDACIs）。HDACIs 可有效抑制体外 MYC 驱动的 MB 细胞的存活，部分原因是诱导 FOXO1 肿瘤抑制基因的表达。HDACIs 还与磷酸肌醇 3-激酶抑制剂协同作用，抑制体内肿瘤生长。这些研究确定了针对最具侵袭性的 MB 形式的有效联合治疗方法。
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