儿童癌症细胞周期抑制剂疗法的最新进展
Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.
作者信息
Mills Christopher C, Kolb E A, Sampson Valerie B
机构信息
University of Delaware, Newark, Delaware.
Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
出版信息
Cancer Res. 2017 Dec 1;77(23):6489-6498. doi: 10.1158/0008-5472.CAN-17-2066. Epub 2017 Nov 2.
Abstract
This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases. .
摘要
本综述描述了细胞周期和检查点调节因子的关键作用，并讨论了用于儿科癌症治疗的特定细胞周期抑制剂的研发情况。文中介绍了药物在儿科患者中的作用机制以及安全性和耐受性，包括靶向CDK4/CDK6的化合物（哌柏西利、瑞博西尼和阿贝西利）、极光激酶（AT9283和MLN8237）、Wee1激酶（MK-1775）、KSP（艾司西肽素）和微管蛋白（紫杉烷类、长春花生物碱）。利用细胞周期阻滞激活的信号相互作用的基于机制的联合用药设计以及针对儿科的药物研发，对于罕见儿童疾病药物的进展至关重要。
相似文献
1
Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.儿童癌症细胞周期抑制剂疗法的最新进展
Cancer Res. 2017 Dec 1;77(23):6489-6498. doi: 10.1158/0008-5472.CAN-17-2066. Epub 2017 Nov 2.
2
CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest.CDK4/6 抑制剂通过可逆的细胞周期阻滞使 Rb 阳性肉瘤细胞对 Wee1 激酶抑制敏感。
Mol Cancer Ther. 2017 Sep;16(9):1751-1764. doi: 10.1158/1535-7163.MCT-17-0040. Epub 2017 Jun 15.
3
Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature.CDK4/6抑制剂的生物学特异性：剂量反应关系、体内信号传导及复合反应特征
Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
4
Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors.来曲唑（LEE011）：这种选择性细胞周期蛋白依赖性激酶 4/6 抑制剂在各种实体瘤中的作用机制和临床影响。
Clin Cancer Res. 2017 Jul 1;23(13):3251-3262. doi: 10.1158/1078-0432.CCR-16-3157. Epub 2017 Mar 28.
5
Progress of CDK4/6 Inhibitor Palbociclib in the Treatment of Cancer.细胞周期蛋白依赖性激酶4/6抑制剂哌柏西利在癌症治疗中的研究进展
Anticancer Agents Med Chem. 2018;18(9):1241-1251. doi: 10.2174/1871521409666170412123500.
6
CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought.CDK4/6 抑制剂：作用机制可能不像以前认为的那么简单。
Cancer Cell. 2018 Jul 9;34(1):9-20. doi: 10.1016/j.ccell.2018.03.023. Epub 2018 May 3.
7
Development of cell-cycle checkpoint therapy for solid tumors.实体瘤细胞周期检查点疗法的研发。
Jpn J Clin Oncol. 2015 Dec;45(12):1097-102. doi: 10.1093/jjco/hyv131. Epub 2015 Oct 20.
8
Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib.细胞周期蛋白依赖性激酶 4/6 抑制剂在乳腺癌中的应用：帕博西尼、瑞博西尼和阿贝西利。
Breast Cancer Res Treat. 2017 Nov;166(1):41-54. doi: 10.1007/s10549-017-4385-3. Epub 2017 Jul 24.
9
Immunomodulation by anticancer cell cycle inhibitors.抗癌细胞周期抑制剂的免疫调节作用。
Nat Rev Immunol. 2020 Nov;20(11):669-679. doi: 10.1038/s41577-020-0300-y. Epub 2020 Apr 28.
10
[Cell cycle inhibitors in endocrine receptor positive breast cancer].[内分泌受体阳性乳腺癌中的细胞周期抑制剂]
Bull Cancer. 2017 Feb;104(2):114-122. doi: 10.1016/j.bulcan.2016.12.005. Epub 2017 Jan 23.
引用本文的文献
1
Reversible and effective cell cycle synchronization method for studying stage-specific processes.用于研究阶段特异性过程的可逆且有效的细胞周期同步方法。
Life Sci Alliance. 2025 Mar 4;8(5). doi: 10.26508/lsa.202403000. Print 2025 May.
2
Reversible and effective cell cycle synchronization method for studying stage-specific investigations.用于研究阶段特异性研究的可逆且有效的细胞周期同步方法。
bioRxiv. 2024 Sep 3:2024.09.02.610832. doi: 10.1101/2024.09.02.610832.
3
Anti-tumor effect and hepatotoxicity mechanisms of psoralen.补骨脂素的抗肿瘤作用及肝毒性机制
Front Pharmacol. 2024 Aug 5;15:1442700. doi: 10.3389/fphar.2024.1442700. eCollection 2024.
4
AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma.AVEN：一种具有预后意义的新型致癌生物标志物以及AVEN相关免疫表型在肺腺癌中的意义
Front Mol Biosci. 2023 Oct 16;10:1265359. doi: 10.3389/fmolb.2023.1265359. eCollection 2023.
5
KIF11 serves as a cell cycle mediator in childhood acute lymphoblastic leukemia.KIF11 作为细胞周期调节剂在儿童急性淋巴细胞白血病中发挥作用。
J Cancer Res Clin Oncol. 2023 Nov;149(17):15609-15622. doi: 10.1007/s00432-023-05240-w. Epub 2023 Sep 1.
6
Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.阿糖胞苷-adavosertib 在白血病细胞系增殖和代谢组学终点中的协同相互作用。
Biomed Pharmacother. 2023 Oct;166:115352. doi: 10.1016/j.biopha.2023.115352. Epub 2023 Aug 24.
7
Novel Insights on Human Carbonic Anhydrase Inhibitors Based on Coumalic Acid: Design, Synthesis, Molecular Modeling Investigation, and Biological Studies.基于肉桂酸的新型人碳酸酐酶抑制剂：设计、合成、分子模拟研究和生物学研究。
Int J Mol Sci. 2022 Jul 19;23(14):7950. doi: 10.3390/ijms23147950.
8
Design of DNA Intercalators Based on 4-Carboranyl-1,8-Naphthalimides: Investigation of Their DNA-Binding Ability and Anticancer Activity.基于 4-碳硼烷-1,8-萘酰亚胺的 DNA 插入剂设计：对其 DNA 结合能力和抗癌活性的研究。
Int J Mol Sci. 2022 Apr 21;23(9):4598. doi: 10.3390/ijms23094598.
9
Gene expression profile of THZ1-treated nasopharyngeal carcinoma cell lines indicates its involvement in the inhibition of the cell cycle.THZ1处理的鼻咽癌细胞系的基因表达谱表明其参与细胞周期抑制。
Transl Cancer Res. 2021 Jan;10(1):445-460. doi: 10.21037/tcr-19-2888.
10
Inhibition of the PLK1-Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer.抑制 PLK1 偶联的细胞周期机制可克服结直肠癌对奥沙利铂的耐药性。
Adv Sci (Weinh). 2021 Dec;8(23):e2100759. doi: 10.1002/advs.202100759. Epub 2021 Oct 28.
本文引用的文献
1
Cell-Cycle Therapeutics Come of Age.细胞周期疗法走向成熟。
J Clin Oncol. 2017 Sep 1;35(25):2949-2959. doi: 10.1200/JCO.2016.69.0032. Epub 2017 Jun 3.
2
Incidence and risk factors of febrile neutropenia in patients with non-Hodgkin B-cell lymphoma receiving R-CHOP in a single center in Japan.日本某单中心接受R-CHOP方案治疗的非霍奇金B细胞淋巴瘤患者发热性中性粒细胞减少症的发生率及危险因素
Support Care Cancer. 2017 Nov;25(11):3313-3320. doi: 10.1007/s00520-017-3747-z. Epub 2017 May 27.
3
Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.鉴定靶向微丝肌球蛋白的癌症抑制剂及其与微管药物的协同作用。
Mol Cancer Ther. 2017 Aug;16(8):1555-1565. doi: 10.1158/1535-7163.MCT-16-0873. Epub 2017 May 18.
4
A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.一项关于 CDK4/6 抑制剂瑞博西利（LEE011）在恶性横纹肌样瘤、神经母细胞瘤和其他实体瘤儿科患者中的 I 期研究。
Clin Cancer Res. 2017 May 15;23(10):2433-2441. doi: 10.1158/1078-0432.CCR-16-2898. Epub 2017 Apr 21.
5
Molecular mechanism of G arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells.新型CDK4/CDK6抑制剂LEE011诱导白血病细胞G期阻滞和细胞衰老的分子机制
Cancer Cell Int. 2017 Mar 6;17:35. doi: 10.1186/s12935-017-0405-y. eCollection 2017.
6
Inhibitors of cyclin-dependent kinases as cancer therapeutics.细胞周期蛋白依赖性激酶抑制剂作为癌症治疗药物
Pharmacol Ther. 2017 May;173:83-105. doi: 10.1016/j.pharmthera.2017.02.008. Epub 2017 Feb 5.
7
Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-cell Acute Lymphoblastic Leukemia.T细胞急性淋巴细胞白血病中与CDK4/6抑制剂联用的协同药物组合
Clin Cancer Res. 2017 Feb 15;23(4):1012-1024. doi: 10.1158/1078-0432.CCR-15-2869. Epub 2016 Nov 9.
8
Dual and Inhibition Demonstrates Synergy against Neuroblastoma.双重作用与抑制显示出对神经母细胞瘤的协同作用。
Clin Cancer Res. 2017 Jun 1;23(11):2856-2868. doi: 10.1158/1078-0432.CCR-16-1114. Epub 2016 Dec 16.
9
A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.AT9283（一种极光激酶选择性抑制剂）用于复发或难治性急性白血病儿童的I/II期试验：开展儿童白血病早期临床试验面临的挑战
Pediatr Blood Cancer. 2017 Jun;64(6). doi: 10.1002/pbc.26351. Epub 2016 Dec 1.
10
Integrating mechanisms of response and resistance against the tubulin binding agent Eribulin in preclinical models of osteosarcoma.在骨肉瘤临床前模型中整合对微管蛋白结合剂艾瑞布林的反应和抗性机制。
Oncotarget. 2016 Dec 27;7(52):86594-86607. doi: 10.18632/oncotarget.13358.
Zotero 插件