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Acute myeloid leukemia patients' clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts.急性髓系白血病患者对idasanutlin（RG7388）的临床反应与白血病原始细胞治疗前的MDM2蛋白表达相关。
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Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors.泊沙康唑（一种强 CYP3A4 抑制剂）、两种新片剂制剂和食物对晚期实体瘤患者中 MDM2 拮抗剂 idasanutlin 药代动力学的影响。
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A single-center, open-label study investigating the excretion balance, pharmacokinetics, metabolism, and absolute bioavailability of a single oral dose of [C]-labeled idasanutlin and an intravenous tracer dose of [C]-labeled idasanutlin in a single cohort of patients with solid tumors.一项单中心、开放标签研究，旨在调查单剂量口服[C]标记的伊达司他林和单剂量静脉注射[C]标记的伊达司他林在单一队列的固体瘤患者中的排泄平衡、药代动力学、代谢和绝对生物利用度。
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Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia.间皮素通过增强糖酵解酶和琥珀酸脱氢酶复合物黄素蛋白亚单位 A 的表达促进急性髓系白血病髓样细胞的糖酵解和线粒体呼吸。
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miR-16-5p enhances sensitivity to RG7388 through targeting expression (WIP1) in Childhood Acute Lymphoblastic Leukemia.微小RNA-16-5p通过靶向儿童急性淋巴细胞白血病中的野生型p53诱导磷酸酶1（WIP1）表达增强对RG7388的敏感性。
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BI-907828, a novel potent MDM2 inhibitor, inhibits glioblastoma brain tumor stem cells in vitro and prolongs survival in orthotopic xenograft mouse models.BI-907828，一种新型强效 MDM2 抑制剂，在体外抑制脑肿瘤干细胞，并延长原位异种移植小鼠模型的存活时间。
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本文引用的文献

1
Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.小分子MDM2拮抗剂RG7112治疗白血病的I期试验结果
Clin Cancer Res. 2016 Feb 15;22(4):868-76. doi: 10.1158/1078-0432.CCR-15-0481. Epub 2015 Oct 12.
2
A distinct p53 target gene set predicts for response to the selective p53-HDM2 inhibitor NVP-CGM097.一个独特的p53靶基因集可预测对选择性p53-HDM2抑制剂NVP-CGM097的反应。
Elife. 2015 May 12;4:e06498. doi: 10.7554/eLife.06498.
3
MDM2 antagonist clinical response association with a gene expression signature in acute myeloid leukaemia.MDM2拮抗剂临床反应与急性髓系白血病基因表达特征的关联
Br J Haematol. 2015 Nov;171(3):432-5. doi: 10.1111/bjh.13411. Epub 2015 Apr 8.
4
Complementary versus companion diagnostics: apples and oranges?补充诊断与伴随诊断：风马牛不相及？
Biomark Med. 2015;9(1):25-34. doi: 10.2217/bmm.14.84.
5
Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.MDM2 拮抗剂 RG7112 对 MDM2 扩增、分化良好或去分化脂肪肉瘤患者 P53 通路的影响：探索性机制研究。
Lancet Oncol. 2012 Nov;13(11):1133-40. doi: 10.1016/S1470-2045(12)70474-6. Epub 2012 Oct 17.
6
Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils.癌基因成瘾作为靶向抗癌治疗的基础理论：承诺与风险。
EMBO Mol Med. 2011 Nov;3(11):623-36. doi: 10.1002/emmm.201100176. Epub 2011 Sep 23.
7
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy.小分子MDM2拮抗剂揭示癌症中异常的p53信号传导：对治疗的启示
Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27.
8
In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.通过MDM2小分子拮抗剂在体内激活p53通路。
Science. 2004 Feb 6;303(5659):844-8. doi: 10.1126/science.1092472. Epub 2004 Jan 2.

Acute myeloid leukemia patients' clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts.

作者信息

Reis Bernhard, Jukofsky Lori, Chen Gong, Martinelli Giovanni, Zhong Hua, So W Venus, Dickinson Michael J, Drummond Mark, Assouline Sarit, Hashemyan Maneja, Theron Michel, Blotner Steven, Lee Je-Hwan, Kasner Margaret, Yoon Sung-Soo, Rueger Ruediger, Seiter Karen, Middleton Steven A, Kelly Kevin R, Vey Norbert, Yee Karen, Nichols Gwen, Chen Lin-Chi, Pierceall William E

机构信息

Roche Innovation Center Basel, Roche Pharma Research and Early Development, Switzerland.

Roche Innovation Center New York, Roche Pharma Research and Early Development, NY, USA.

出版信息

Haematologica. 2016 May;101(5):e185-8. doi: 10.3324/haematol.2015.139717. Epub 2016 Feb 11.

DOI:10.3324/haematol.2015.139717
PMID:26869629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5004378/
Abstract
摘要