肿瘤的分化治疗

摘要/Abstract

摘要：

肿瘤细胞有去分化、分化阻断和转分化3种表型可塑，靶向肿瘤细胞可塑的分化治疗已经成为新的肿瘤治疗模式。肿瘤分化治疗应用诱导分化、启动分化和调控分化促进肿瘤细胞向成熟细胞定向分化和重建正常表型，从而实现肿瘤治疗的目的。

岳红云, 张百红. 肿瘤的分化治疗[J]. 国际肿瘤学杂志, 2024, 51(2): 109-113.

Yue Hongyun, Zhang Baihong. Differentiation therapies in human cancers[J]. Journal of International Oncology, 2024, 51(2): 109-113.

图/表1

表1

肿瘤的分化治疗"

细胞可塑	作用机制	药物类型	临床试验
诱导分化	表观遗传剂	EZH2抑制剂，HDAC抑制剂	临床前研究^{[ 10 ⇓ - 12 ]}
	自噬诱导剂	ULK1抑制剂	临床前研究^{[ 13 ]}
	干性调节剂	SOX2抑制剂，Wnt抑制剂，MEK抑制剂，erastin	临床前研究^{[ 15 ⇓ - 17 ]}
启动分化	代谢调节剂	Vorasidenib	Ⅱ期^{[ 20 - 21 ]}
	转录因子调节剂	SOX10拮抗剂	临床前研究^{[ 25 ]}
	免疫细胞分化剂	抗PD-1/PD-L1抗体	临床应用^{[ 27 - 28 ]}
调控分化	染色质可塑剂	Exportin1抑制剂，LSD1抑制剂	临床前研究^{[ 33 ⇓ - 35 ]}
	血管生成抑制剂	瑞格非尼	临床应用^{[ 36 ]}
	生长信号阻断剂	ZNF117	临床前研究^{[ 38 ]}
	衰老细胞清除剂	抗PD-1/PD-L1抗体	临床应用^{[ 42 ]}

表1

参考文献45

[1]	Pérez-González A. Bévant K, Blanpain C. Cancer cell plasticity during tumor progression, metastasis and response to therapy[J].Nat Cancer,2023,4(8): 1063-1082. DOI:10.1038/s43018-023-00595-y.
[2]	Yuan S, Norgard RJ, Stanger BZ. Cellular plasticity in cancer[J].Cancer Discov,2019,9(7): 837-851. DOI:10.1158/2159-8290.CD-19-0015. pmid:30992279
[3]	Hanahan D. Hallmarks of cancer: new dimensions[J].Cancer Discov,2022,12(1): 31-46. DOI:10.1158/2159-8290.CD-21-1059. pmid:35022204
[4]	de Thé H. Differentiation therapy revisited[J].Nat Rev Cancer,2018,18(2): 117-127. DOI:10.1038/nrc.2017.103. pmid:29192213
[5]	Barker N, Ridgway RA, van Es JH, et al. Crypt stem cells as the cells-of-origin of intestinal cancer[J].Nature,2009,457(7229): 608-611. DOI:10.1038/nature07602.
[6]	Belote RL, Le D, Maynard A, et al. Human melanocyte development and melanoma dedifferentiation at single-cell resolution[J].Nat Cell Biol,2021,23(9): 1035-1047. DOI:10.1038/s41556-021-00740-8. pmid:34475532
[7]	Kozono S, Lin YM, Seo HS, et al. Arsenic targets Pin1 and coope-rates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells[J].Nat Commun,2018,9(1): 3069. DOI:10.1038/s41467-018-05402-2.
[8]	Davalos V, Esteller M. Cancer epigenetics in clinical practice[J].CA Cancer J Clin,2023,73(4): 376-424. DOI:10.3322/caac.21765.
[9]	Feinberg AP, Levchenko A. Epigenetics as a mediator of plasticity in cancer[J].Science,2023,379(6632): eaaw3835. DOI:10.1126/science.aaw3835.
[10]	Ferrarelli LK. Exploiting an epigenetic Switch in adrenal cancer[J].Sci Signal,2023,16(794): 10. DOI:10.1126/scisignal.adj7203.
[11]	Xie J, Wang Z, Fan W, et al. Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma[J].Signal Transduct Target Ther,2021,6(1): 333. DOI:10.1038/s41392-021-00702-4.
[12]	Anastas JN, Zee BM, Kalin JH, et al. Re-programing chromatin with a bifunctional LSD1/HDAC inhibitor induces therapeutic differentiation in DIPG[J].Cancer Cell,2019,36(5): 528-544.e10. DOI:10.1016/j.ccell.2019.09.005. pmid:31631026
[13]	Ianniciello A, Zarou MM, Rattigan KM, et al. ULK1 inhibition promotes oxidative stress-induced differentiation and sensitizes leukemic stem cells to targeted therapy[J].Sci Transl Med,2021,13(613): eabd5016. DOI:10.1126/scitranslmed.abd5016.
[14]	Tan SH, Barker N. Stemming colorectal cancer growth and metastasis: HOXA5 forces cancer stem cells to differentiate[J].Cancer Cell,2015,28(6): 683-685. DOI:10.1016/j.ccell.2015.11.004. pmid:26678334
[15]	Zhan TZ, Ambrosi G, Wandmacher AM, et al. MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer[J].Nat Commun,2019,10(1): 2197. DOI:10.1038/s41467-019-09898-0.
[16]	Fang XG, Huang Z, Zhai K, et al. Inhibiting DNA-PK induces glioma stem cell differentiation and sensitizes glioblastoma to radiation in mice[J].Sci Transl Med,2021,13(600): eabc7275. DOI:10.1126/scitranslmed.abc7275.
[17]	Kemeny LV, Fisher DE. Targeting the (Un)differentiated State of Cancer[J].Cancer Cell,2018,33(5): 793-795. DOI:10.1016/j.ccell.2018.04.007. pmid:29763619
[18]	Malta TM, Sokolov A, Gentles AJ, et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation[J].Cell,2018,173(2): 338-354.e15. DOI:10.1016/j.cell.2018.03.034. pmid:29625051
[19]	Saha SK, Parachoniak CA, Ghanta KS, et al. Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer[J].Nature,2014,513(7516): 110-114. DOI:10.1038/nature13441.
[20]	Molenaar RJ, Wilmink JW. IDH1/2 mutations in cancer stem cells and their implications for differentiation therapy[J].J Histochem Cytochem,2022,70(1): 83-97. DOI:10.1369/00221554211062499. pmid:34967233
[21]	Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma[J].N Engl J Med,2023,389(7): 589-601. DOI:10.1056/NEJMoa2304194.
[22]	Morris JP 4th, Yashinskie JJ, Koche R, et al. α-Ketoglutarate links p53 to cell fate during tumour suppression[J].Nature,2019,573(7775): 595-599. DOI:10.1038/s41586-019-1577-5.
[23]	Tran TQ, Hanse EA, Habowski AN, et al. α-Ketoglutarate atte-nuates Wnt signaling and drives differentiation in colorectal cancer[J].Nat Cancer,2020,1(3): 345-358. DOI:10.1038/s43018-020-0035-5.
[24]	Kaufman CK, Mosimann C, Fan ZP, et al. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation[J].Science,2016,351(6272): aad2197. DOI:10.1126/science.aad2197.
[25]	Capparelli C, Purwin TJ, Glasheen M, et al. Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma[J].Nat Commun,2022,13(1): 1381. DOI:10.1038/s41467-022-28801-y. pmid:35296667
[26]	Henning AN, Klebanoff CA, Restifo NP. Silencing stemness in T cell differentiation[J].Science,2018,359(6372): 163-164. DOI:10.1126/science.aar5541. pmid:29326263
[27]	Gill AL, Wang PH, Lee J, et al. PD-1 blockade increases the self-renewal of stem-like CD8 T cells to compensate for their accelerated differentiation into effectors[J].Sci Immunol,2023,8(86): eadg0539. DOI:10.1126/sciimmunol.adg0539.
[28]	Castiglioni A, Yang Y, Williams K, et al. Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors[J].Nat Commun,2023,14(1): 4703. DOI:10.1038/s41467-023-40398-4. pmid:37543621
[29]	Collins SM, Alexander KA, Lundh S, et al. TOX2 coordinates with TET2 to positively regulate central memory differentiation in human CAR T cells[J].Sci Adv,2023,9(29): eadh2605. DOI:10.1126/sciadv.adh2605.
[30]	Burdziak C, Alonso-Curbelo D, Walle T, et al. Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumori-genesis[J].Science,2023,380(6645): eadd5327. DOI:10.1126/science.add5327.
[31]	Rüland L, Andreatta F, Massalini S, et al. Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss[J].Nat Commun,2023,14(1): 2377. DOI:10.1038/s41467-023-37951-6. pmid:37137901
[32]	Kim MR, Wu MJ, Zhang YS, et al. TET2 directs mammary luminal cell differentiation and endocrine response[J].Nat Commun,2020,11(1): 4642. DOI:10.1038/s41467-020-18129-w. pmid:32934200
[33]	Quintanal-Villalonga A, Durani V, Sabet A, et al. Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers[J].Sci Transl Med,2023,15(707): eadf7006. DOI:10.1126/scitranslmed.adf7006.
[34]	Duplaquet L, Li Y, Booker M, et al. KDM6A epigenetically regulates subtype plasticity in small cell lung cancer[J].Nat Cell Biol,2023,25(9): 1346-1358. DOI:10.1038/s41556-023-01210-z. pmid:37591951
[35]	Chen HY, Durmaz YT, Li Y, et al. Regulation of neuroendocrine plasticity by the RNA-binding protein ZFP36L1[J].Nat Commun,2022,13(1): 4998. DOI:10.1038/s41467-022-31998-7.
[36]	Deshors P, Arnauduc F, Boëlle B, et al. Impact of regorafenib on endothelial transdifferentiation of glioblastoma stem-like cells[J].Cancers (Basel),2022,14(6):1551. DOI:10.3390/cancers14061551.
[37]	Chan JM, Zaidi S, Love JR, et al. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling[J].Science,2022,377(6611): 1180-1191. DOI:10.1126/science.abn0478.
[38]	Liu J, Wang X, Chen AT, et al. ZNF117 regulates glioblastoma stem cell differentiation towards oligodendroglial lineage[J].Nat Commun,2022,13(1): 2196. DOI:10.1038/s41467-022-29884-3.
[39]	Bala P, Rennhack JP, Aitymbayev D, et al. Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation[J].Sci Adv,2023,9(13): eadf0927. DOI:10.1126/sciadv.adf0927.
[40]	Boumahdi S, de Sauvage FJ. The great escape: tumour cell plasticity in resistance to targeted therapy[J].Nat Rev Drug Discov,2020,19(1): 39-56. DOI:10.1038/s41573-019-0044-1. pmid:31601994
[41]	Schmitt CA, Wang B, Demaria M. Senescence and cancer-role and therapeutic opportunities[J].Nat Rev Clin Oncol,2022,19(10): 619-636. DOI:10.1038/s41571-022-00668-4.
[42]	Wang TW, Johmura Y, Suzuki N, et al. Blocking PD-L1-PD-1 improves senescence surveillance and ageing phenotypes[J].Nature,2022,611(7935): 358-364. DOI:10.1038/s41586-022-05388-4.
[43]	张百红, 岳红云. 肿瘤休眠的周期和意义[J].现代肿瘤医学,2023,31(2): 392-394. DOI:10.3969/j.issn.1672-4992.2023.02.039.
[44]	Shen S, Vagner S, Robert C. Persistent cancer cells: the deadly survivors[J].Cell,2020,183(4): 860-874. DOI:10.1016/j.cell.2020.10.027. pmid:33186528
[45]	Lyko F. Distal memory in wound healing and cancer[J].Nat Cell Biol,2023,25(5): 631-632. DOI:10.1038/s41556-023-01132-w. pmid:37081166

Differentiation therapies in human cancers

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表1

参考文献45

相关文章15

编辑推荐

Metrics

本文评价

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲.血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊.局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华.Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青.血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺.PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云.新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚.EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵.抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六.基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六.肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东.ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅.基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳.炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝.癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志.宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.