Abstract
In recent years, dysregulation of the notch pathway has been associated with the development and progression of various cancers. Notch signaling is involved in several cellular processes, such as proliferation, differentiation, apoptosis, and angiogenesis, and its abnormal activation can lead to uncontrolled cell growth and tumorigenesis. In various human cancers, the Notch pathway has been shown to have both tumor-promoting and tumor-suppressive effects, depending on the context and stage of cancer development. Notch signaling has been implicated in tumor initiation, cancer cell proliferation, cell migration and maintenance of cancer stem cells in several human cancers, including leukemia, breast, pancreatic and lung cancer. Understanding the role of the Notch pathway in cancer development and progression may provide new opportunities for the development of potent targeted therapies for cancer treatment. Several drugs targeting the Notch pathway are currently in preclinical or clinical development and may hold promise for anticancer therapy in the future.
Graphical Abstract
[http://dx.doi.org/10.1016/j.canlet.2015.07.048] [PMID: 26341688]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3958] [PMID: 17332312]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1890] [PMID: 15781650]
[http://dx.doi.org/10.1038/sj.bjc.6605451] [PMID: 19953094]
[http://dx.doi.org/10.1155/2020/6768942] [PMID: 32211044]
[http://dx.doi.org/10.1111/bjh.14869] [PMID: 28771672]
[http://dx.doi.org/10.1111/bjh.17940] [PMID: 34792186]
[http://dx.doi.org/10.3390/cells9061549] [PMID: 32630477]
[http://dx.doi.org/10.1242/dev.172148] [PMID: 30709911]
[http://dx.doi.org/10.1371/journal.pone.0123016] [PMID: 25849484]
[http://dx.doi.org/10.2147/OTT.S165144] [PMID: 30127625]
[http://dx.doi.org/10.1016/j.yexcr.2019.111682] [PMID: 31634483]
[http://dx.doi.org/10.18632/oncotarget.7964] [PMID: 26967055]
[http://dx.doi.org/10.3892/or.2022.8397] [PMID: 36069229]
[http://dx.doi.org/10.1098/rsob.190187] [PMID: 31690218]
[http://dx.doi.org/10.1038/s41598-019-56536-2] [PMID: 31882986]
[http://dx.doi.org/10.1146/annurev-pathol-052016-100127] [PMID: 27959635]
[http://dx.doi.org/10.1186/s12935-021-02026-3] [PMID: 34167524]
[http://dx.doi.org/10.1038/mto.2016.18] [PMID: 27525306]
[http://dx.doi.org/10.1016/j.taap.2022.115988] [PMID: 35307375]
[http://dx.doi.org/10.1186/s12943-017-0709-5]
[PMID: 32139432]
[http://dx.doi.org/10.1080/14656566.2022.2033725] [PMID: 35193450]
[http://dx.doi.org/10.1002/jcp.30099] [PMID: 33174211]
[http://dx.doi.org/10.3390/cancers14122997] [PMID: 35740661]
[http://dx.doi.org/10.1158/0008-5472.CAN-18-1617] [PMID: 30563887]
[http://dx.doi.org/10.3390/cancers11121958] [PMID: 31817634]
[http://dx.doi.org/10.1182/blood-2018-99-118701]
[http://dx.doi.org/10.1038/s41467-022-31160-3] [PMID: 35710644]
[http://dx.doi.org/10.4049/jimmunol.2000889] [PMID: 33397738]
[http://dx.doi.org/10.1186/s12929-021-00732-8] [PMID: 33966637]
[http://dx.doi.org/10.1186/s12935-022-02736-2] [PMID: 36229883]
[http://dx.doi.org/10.1016/j.phymed.2022.153972] [PMID: 35151214]
[http://dx.doi.org/10.1186/s13045-020-00901-6] [PMID: 32456660]
[http://dx.doi.org/10.3390/cells9061392] [PMID: 32503256]
[http://dx.doi.org/10.21037/sci.2019.08.08] [PMID: 31559312]
[http://dx.doi.org/10.1038/s41392-022-00922-2] [PMID: 35246503]
[http://dx.doi.org/10.1038/s41419-018-0810-8] [PMID: 30038258]
[http://dx.doi.org/10.1186/s13578-019-0361-4] [PMID: 31827763]
[http://dx.doi.org/10.1038/nature22323] [PMID: 28489825]
[http://dx.doi.org/10.21037/sci.2018.02.02] [PMID: 29682512]
[http://dx.doi.org/10.1038/s43018-021-00181-0]
[http://dx.doi.org/10.1111/jcmm.15990] [PMID: 33073486]
[http://dx.doi.org/10.2174/1389450118666170309143419] [PMID: 28294046]
[PMID: 28337369]
[http://dx.doi.org/10.3389/fcell.2021.692173] [PMID: 34295896]
[http://dx.doi.org/10.21037/atm-22-1041] [PMID: 35434013]
[http://dx.doi.org/10.3906/biy-1808-58] [PMID: 30930637]
[http://dx.doi.org/10.1016/j.biopha.2021.111496] [PMID: 33743335]
[http://dx.doi.org/10.1080/14728222.2019.1641198] [PMID: 31304807]
[http://dx.doi.org/10.1177/0022034518760297] [PMID: 29489439]
[http://dx.doi.org/10.1007/s13402-019-00441-3] [PMID: 30968324]
[http://dx.doi.org/10.3389/fonc.2018.00550] [PMID: 30534535]
[http://dx.doi.org/10.1007/s40618-017-0715-x] [PMID: 28653287]
[http://dx.doi.org/10.1038/s41467-017-00204-4] [PMID: 28747678]
[http://dx.doi.org/10.1155/2021/4739868] [PMID: 34925644]
[http://dx.doi.org/10.1080/15384101.2017.1312237] [PMID: 28388267]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0286] [PMID: 28827371]
[http://dx.doi.org/10.1155/2019/5470470] [PMID: 31915510]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2358] [PMID: 28153862]
[http://dx.doi.org/10.1126/scitranslmed.aal3322] [PMID: 28724574]
[http://dx.doi.org/10.1016/j.bbrc.2018.06.097] [PMID: 29932924]
[http://dx.doi.org/10.3390/cancers12113142] [PMID: 33120947]
[http://dx.doi.org/10.3892/ijmm.2016.2689] [PMID: 27460529]
[http://dx.doi.org/10.1016/j.yexcr.2019.111806] [PMID: 31891681]
[http://dx.doi.org/10.1080/15384047.2016.1250985] [PMID: 27791463]
[PMID: 27115169]
[http://dx.doi.org/10.1007/s13402-022-00663-y] [PMID: 35357654]
[http://dx.doi.org/10.1002/rmv.1988] [PMID: 29956408]
[http://dx.doi.org/10.1158/0008-5472.CAN-18-0451] [PMID: 30154153]
[http://dx.doi.org/10.1007/s00109-018-1724-8] [PMID: 30483821]
[http://dx.doi.org/10.1016/j.wneu.2019.07.180] [PMID: 31376551]
[http://dx.doi.org/10.2174/1574892816666210607092350] [PMID: 34109915]
[http://dx.doi.org/10.1038/s41417-019-0122-x] [PMID: 31308481]
[http://dx.doi.org/10.3389/fcell.2021.673873] [PMID: 34692669]
[http://dx.doi.org/10.1186/s13742-015-0107-0] [PMID: 26759717]
[http://dx.doi.org/10.1016/j.jnutbio.2021.108843] [PMID: 34407449]
[http://dx.doi.org/10.3390/cancers11050630] [PMID: 31064120]
[http://dx.doi.org/10.1186/s12885-022-09414-6] [PMID: 35351071]
[http://dx.doi.org/10.1016/j.jsbmb.2019.02.008] [PMID: 30817989]
[http://dx.doi.org/10.1073/pnas.2216901120] [PMID: 36893267]
[http://dx.doi.org/10.1158/1535-7163.MCT-22-0243] [PMID: 36223541]
[http://dx.doi.org/10.1016/j.biopha.2023.114248] [PMID: 36645960]
[http://dx.doi.org/10.1007/s12032-022-01905-7] [PMID: 36662310]
[http://dx.doi.org/10.3389/fonc.2023.1078768] [PMID: 36798826]