用于癌症治疗的DNA低甲基化药物
DNA Hypomethylating Drugs in Cancer Therapy.
作者信息
Sato Takahiro, Issa Jean-Pierre J, Kropf Patricia
机构信息
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania 19111.
出版信息
Cold Spring Harb Perspect Med. 2017 May 1;7(5):a026948. doi: 10.1101/cshperspect.a026948.
Abstract
Aberrant DNA methylation is a critically important modification in cancer cells, which, through promoter and enhancer DNA methylation changes, use this mechanism to activate oncogenes and silence of tumor-suppressor genes. Targeting DNA methylation in cancer using DNA hypomethylating drugs reprograms tumor cells to a more normal-like state by affecting multiple pathways, and also sensitizes these cells to chemotherapy and immunotherapy. The first generation hypomethylating drugs azacitidine and decitabine are routinely used for the treatment of myeloid leukemias and a next-generation drug (guadecitabine) is currently in clinical trials. This review will summarize preclinical and clinical data on DNA hypomethylating drugs as a cancer therapy.
摘要
异常的DNA甲基化是癌细胞中至关重要的修饰，它通过启动子和增强子DNA甲基化变化，利用这种机制激活癌基因并使肿瘤抑制基因沉默。使用DNA低甲基化药物靶向癌症中的DNA甲基化，通过影响多种途径将肿瘤细胞重编程为更接近正常的状态，还能使这些细胞对化疗和免疫疗法敏感。第一代低甲基化药物阿扎胞苷和地西他滨常用于治疗髓系白血病，下一代药物（胍地西他滨）目前正在进行临床试验。本综述将总结DNA低甲基化药物作为癌症治疗的临床前和临床数据。
相似文献
1
DNA Hypomethylating Drugs in Cancer Therapy.
Cold Spring Harb Perspect Med. 2017 May 1;7(5):a026948. doi: 10.1101/cshperspect.a026948.
2
DNA methylation in haematological malignancies: the role of decitabine.
Expert Opin Investig Drugs. 2003 Dec;12(12):1985-93. doi: 10.1517/13543784.12.12.1985.
3
The use of hypomethylating agents in the treatment of hematologic malignancies.
Leuk Lymphoma. 2007 Sep;48(9):1676-95. doi: 10.1080/10428190701493910.
4
Will next-generation agents deliver on the promise of epigenetic hypomethylation therapy?
Epigenomics. 2015 Oct;7(7):1083-8. doi: 10.2217/epi.15.66. Epub 2015 Nov 6.
5
Azacitidine Use for Myeloid Neoplasms.
Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):e147-e155. doi: 10.1016/j.clml.2018.02.005. Epub 2018 Feb 8.
6
Decitabine and its role in the treatment of hematopoietic malignancies.
Leuk Lymphoma. 2007 Aug;48(8):1472-81. doi: 10.1080/10428190701471981.
7
The role of hypomethylating agents in the treatment of elderly patients with AML.
J Geriatr Oncol. 2014 Jan;5(1):89-105. doi: 10.1016/j.jgo.2013.08.004. Epub 2013 Sep 24.
8
Development, validation, and clinical application of a high-performance liquid chromatography-tandem mass spectrometry assay for the quantification of total intracellular β-decitabine nucleotides and genomic DNA incorporated β-decitabine and 5-methyl-2'-deoxycytidine.
J Pharm Biomed Anal. 2019 Feb 5;164:16-26. doi: 10.1016/j.jpba.2018.10.001. Epub 2018 Oct 3.
9
[Hypomethylating agents for the treatment of myelodysplastic syndromes].
Bull Cancer. 2011 Aug;98(8):927-34. doi: 10.1684/bdc.2011.1411.
10
Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia.
Leuk Lymphoma. 2010 Dec;51(12):2275-84. doi: 10.3109/10428194.2010.528093. Epub 2010 Nov 15.
引用本文的文献
1
DNA methylation protects cancer cells against senescence.
Nat Commun. 2025 Jul 1;16(1):5901. doi: 10.1038/s41467-025-61157-7.
2
GSK-3484862, a DNMT1 degrader, promotes expression in lung cancer cells.
NAR Cancer. 2025 May 27;7(2):zcaf018. doi: 10.1093/narcan/zcaf018. eCollection 2025 Jun.
3
A CRISPR-Cas9 screen reveals genetic determinants of the cellular response to decitabine.
EMBO Rep. 2025 Mar;26(6):1528-1565. doi: 10.1038/s44319-025-00385-w. Epub 2025 Feb 10.
4
Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.
Epigenetics. 2025 Dec;20(1):2451551. doi: 10.1080/15592294.2025.2451551. Epub 2025 Feb 2.
5
A multiomics approach reveals RNA dynamics promote cellular sensitivity to DNA hypomethylation.
Sci Rep. 2024 Oct 29;14(1):25940. doi: 10.1038/s41598-024-77314-9.
6
Quinoline-based compounds can inhibit diverse enzymes that act on DNA.
Cell Chem Biol. 2024 Dec 19;31(12):2112-2127.e6. doi: 10.1016/j.chembiol.2024.09.007. Epub 2024 Oct 21.
7
Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment.
Int J Mol Sci. 2024 Aug 30;25(17):9460. doi: 10.3390/ijms25179460.
8
Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review).
Mol Clin Oncol. 2024 Jun 28;21(3):59. doi: 10.3892/mco.2024.2757. eCollection 2024 Sep.
9
Venetoclax therapy and emerging resistance mechanisms in acute myeloid leukaemia.
Cell Death Dis. 2024 Jun 12;15(6):413. doi: 10.1038/s41419-024-06810-7.
10
A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.
Oncogene. 2024 Jun;43(23):1727-1741. doi: 10.1038/s41388-024-03054-9. Epub 2024 May 8.
本文引用的文献
1
Targeting Calcium Signaling Induces Epigenetic Reactivation of Tumor Suppressor Genes in Cancer.
Cancer Res. 2016 Mar 15;76(6):1494-505. doi: 10.1158/0008-5472.CAN-14-2391. Epub 2015 Dec 30.
2
Hypomethylation of TET2 Target Genes Identifies a Curable Subset of Acute Myeloid Leukemia.
J Natl Cancer Inst. 2015 Nov 13;108(2):djv323. doi: 10.1093/jnci/djv323.
3
Minimal role of base excision repair in TET-induced global DNA demethylation in HEK293T cells.
Epigenetics. 2015;10(11):1006-13. doi: 10.1080/15592294.2015.1091145.
4
Epigenetic synergy between decitabine and platinum derivatives.
Clin Epigenetics. 2015 Sep 11;7(1):97. doi: 10.1186/s13148-015-0131-z. eCollection 2015.
5
A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.
Leukemia. 2016 Feb;30(2):268-73. doi: 10.1038/leu.2015.244. Epub 2015 Sep 14.
6
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses.
Cell. 2015 Aug 27;162(5):974-86. doi: 10.1016/j.cell.2015.07.011.
7
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.
Cell. 2015 Aug 27;162(5):961-73. doi: 10.1016/j.cell.2015.07.056.
8
Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.
Lancet Oncol. 2015 Sep;16(9):1099-1110. doi: 10.1016/S1470-2045(15)00038-8. Epub 2015 Aug 19.
9
SGI-110: DNA Methyltransferase Inhibitor Oncolytic.
Drugs Future. 2013 Aug;38(8):535-543.
10
A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC.
Cancer Cell. 2015 Jul 13;28(1):57-69. doi: 10.1016/j.ccell.2015.06.002.
Zotero 插件