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2000
Volume 25, Issue 22
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Cancer and Alzheimer's disease (AD) are among the most prevalent diseases in contemporary society, exerting profound psychological and physical distress on affected individuals and their kin. There is an emerging consensus from epidemiological studies suggesting a potential inverse relationship between the two conditions; that is, the presence of one disease might offer some level of protection against the other. The etiology of both cancer and AD is intricately linked to dysregulation and perturbations in critical signaling pathways. These pathways, along with the diverse factors they encompass, exert distinct influences on the pathogenesis of two diseases. In this paper, we make a short review of the different mutations in the relevant signaling pathways between cancer and AD and introduce a few representative drugs for the two diseases based on various targets to provide a new idea for treating cancer and AD.

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2025-03-07
2025-12-28

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References

  1. SiegelR.L. MillerK.D. FuchsH.E. JemalA. Cancer Statistics, 2021.CA Cancer J. Clin.202171173310.3322/caac.21654 33433946
     [Google Scholar]
  2. HausmanD.M. What is Cancer?Perspect. Biol. Med.201962477878410.1353/pbm.2019.0046 31761807
     [Google Scholar]
  3. HanahanD. WeinbergR.A. Hallmarks of cancer: The next generation.Cell2011144564667410.1016/j.cell.2011.02.013 21376230
     [Google Scholar]
  4. KroemerG. PouyssegurJ. Tumor cell metabolism: Cancer’s Achilles’ heel.Cancer Cell200813647248210.1016/j.ccr.2008.05.005 18538731
     [Google Scholar]
  5. HodsonR. Alzheimer’s disease.Nature20185597715S110.1038/d41586‑018‑05717‑6 30046078
     [Google Scholar]
  6. CheclerF. Alves da CostaC. p53 in neurodegenerative diseases and brain cancers.Pharmacol. Ther.201414219911310.1016/j.pharmthera.2013.11.009 24287312
     [Google Scholar]
  7. BarkerR.M. HollyJ.M.P. BiernackaK.M. Allen-BirtS.J. PerksC.M. Mini review: Opposing pathologies in cancer and Alzheimer’s disease: Does the PI3K/Akt pathway provide clues?Front. Endocrinol.20201140310.3389/fendo.2020.00403 32655497
     [Google Scholar]
  8. KaliaM. Dysphagia and aspiration pneumonia in patients with Alzheimer’s disease.Metabolism20035210Suppl. 2363810.1016/S0026‑0495(03)00300‑7 14577062
     [Google Scholar]
  9. KhanS. BarveK.H. KumarM.S. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease.Curr. Neuropharmacol.202018111106112510.2174/1570159X18666200528142429 32484110
     [Google Scholar]
  10. IbáñezK. BoullosaC. Tabarés-SeisdedosR. BaudotA. ValenciaA. Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.PLoS Genet.2014102e100417310.1371/journal.pgen.1004173 24586201
     [Google Scholar]
  11. ZhangD.D. OuY.N. YangL. MaY.H. TanL. FengJ.F. ChengW. YuJ.T. Investigating the association between cancer and dementia risk: A longitudinal cohort study.Alzheimers Res. Ther.202214114610.1186/s13195‑022‑01090‑9 36199128
     [Google Scholar]
  12. ChamberlainJ.D. RouanetA. DuboisB. PasquierF. HanonO. GabelleA. CeccaldiM. Krolak-SalmonP. BéjotY. GodefroyO. WallonD. GentricA. ChêneG. DufouilC. Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.Alzheimers Dement.20211791415142110.1002/alz.12308 33656287
     [Google Scholar]
  13. MusiccoM. AdorniF. Di SantoS. PrinelliF. PettenatiC. CaltagironeC. PalmerK. RussoA. Inverse occurrence of cancer and Alzheimer disease.Neurology201381432232810.1212/WNL.0b013e31829c5ec1 23843468
     [Google Scholar]
  14. BurkeW.J. Cancer linked to Alzheimer disease but not vascular dementia.Neurology201075131216 20922823
     [Google Scholar]
  15. NusseR. CleversH. Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities.Cell2017169698599910.1016/j.cell.2017.05.016 28575679
     [Google Scholar]
  16. BugterJ.M. FendericoN. MauriceM.M. Mutations and mechanisms of WNT pathway tumour suppressors in cancer.Nat. Rev. Cancer202121152110.1038/s41568‑020‑00307‑z 33097916
     [Google Scholar]
  17. ParsonsM.J. TammelaT. DowL.E. WNT as a driver and dependency in Cancer.Cancer Discov.202111102413242910.1158/2159‑8290.CD‑21‑0190 34518209
     [Google Scholar]
  18. MarquardtJ.U. SeoD. AndersenJ.B. GillenM.C. KimM.S. ConnerE.A. GalleP.R. FactorV.M. ParkY.N. ThorgeirssonS.S. Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits.J. Hepatol.201460234635310.1016/j.jhep.2013.10.014 24512821
     [Google Scholar]
  19. ZhuM. LuT. JiaY. LuoX. GopalP. LiL. OdewoleM. RenteriaV. SingalA.G. JangY. GeK. WangS.C. SorouriM. ParekhJ.R. MacConmaraM.P. YoppA.C. WangT. ZhuH. Somatic mutations increase hepatic clonal fitness and regeneration in chronic liver disease.Cell20191773608621.e1210.1016/j.cell.2019.03.026 30955891
     [Google Scholar]
  20. LeeY. LeeJ.K. AhnS.H. LeeJ. NamD.H. WNT signaling in glioblastoma and therapeutic opportunities.Lab. Invest.201696213715010.1038/labinvest.2015.140 26641068
     [Google Scholar]
  21. JiaL. Piña-CrespoJ. LiY. Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer’s disease.Mol. Brain201912110410.1186/s13041‑019‑0525‑5 31801553
     [Google Scholar]
  22. MarchettiB. Wnt/β-Catenin signaling pathway governs a full program for dopaminergic neuron survival, neurorescue and regeneration in the MPTP mouse model of Parkinson’s disease.Int. J. Mol. Sci.20181912374310.3390/ijms19123743 30477246
     [Google Scholar]
  23. BuechlerJ. SalinasP.C. Deficient Wnt signaling and synaptic vulnerability in Alzheimer’s disease: Emerging roles for the LRP6 receptor.Front. Synaptic Neurosci.2018103810.3389/fnsyn.2018.00038 30425633
     [Google Scholar]
  24. YangY. ZhangZ. Microglia and Wnt pathways: Prospects for inflammation in Alzheimer’s disease.Front. Aging Neurosci.20201211010.3389/fnagi.2020.00110 32477095
     [Google Scholar]
  25. WangQ. HuangX. SuY. YinG. WangS. YuB. LiH. QiJ. ChenH. ZengW. ZhangK. VerkhratskyA. NiuJ. YiC. Activation of Wnt/β-catenin pathway mitigates blood–brain barrier dysfunction in Alzheimer’s disease.Brain2022145124474448810.1093/brain/awac236 35788280
     [Google Scholar]
  26. LiuC.C. TsaiC.W. DeakF. RogersJ. PenuliarM. SungY.M. MaherJ.N. FuY. LiX. XuH. EstusS. HoeH.S. FryerJ.D. KanekiyoT. BuG. Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer’s disease.Neuron2014841637710.1016/j.neuron.2014.08.048 25242217
     [Google Scholar]
  27. InestrosaN.C. Tapia-RojasC. LindsayC.B. ZolezziJ.M. Wnt signaling pathway dysregulation in the aging brain: Lessons from the Octodon degus.Front. Cell Dev. Biol.2020873410.3389/fcell.2020.00734 32850846
     [Google Scholar]
  28. MartínezM. InestrosaN.C. The transcriptional landscape of Alzheimer’s disease and its association with Wnt signaling pathway.Neurosci. Biobehav. Rev.202112845446610.1016/j.neubiorev.2021.06.029 34224789
     [Google Scholar]
  29. TayL. LeungB. YeoA. ChanM. LimW.S. Elevations in Serum Dickkopf-1 and disease progression in community-dwelling older adults with mild cognitive impairment and mild-to-moderate Alzheimer’s disease.Front. Aging Neurosci.20191127810.3389/fnagi.2019.00278 31680933
     [Google Scholar]
  30. LiuJ.F. ZhouX.K. ChenJ.H. YiG. ChenH.G. BaM.C. LinS.Q. QiY.C. Up-regulation of PIK3CA promotes metastasis in gastric carcinoma.World J. Gastroenterol.201016394986499110.3748/wjg.v16.i39.4986 20954287
     [Google Scholar]
  31. Akagi, Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma.Int. J. Oncol.2009343
     [Google Scholar]
  32. ThorpeL.M. YuzugulluH. ZhaoJ.J. PI3K in cancer: Divergent roles of isoforms, modes of activation and therapeutic targeting.Nat. Rev. Cancer201515172410.1038/nrc3860 25533673
     [Google Scholar]
  33. DanielP.M. FilizG. BrownD.V. ChristieM. WaringP.M. ZhangY. HaynesJ.M. PoutonC. FlanaganD. VincanE. JohnsT.G. MontgomeryK. PhillipsW.A. MantamadiotisT. PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein.Neuro-oncol.201820101344135510.1093/neuonc/noy068 29718345
     [Google Scholar]
  34. ChenC.J. SgrittaM. MaysJ. ZhouH. LuceroR. ParkJ. WangI.C. ParkJ.H. KaipparettuB.A. StoicaL. Jafar-NejadP. RigoF. ChinJ. NoebelsJ.L. Costa-MattioliM. Therapeutic inhibition of mTORC2 rescues the behavioral and neurophysiological abnormalities associated with Pten-deficiency.Nat. Med.201925111684169010.1038/s41591‑019‑0608‑y 31636454
     [Google Scholar]
  35. FedeleC.G. OomsL.M. HoM. VieusseuxJ. O’TooleS.A. MillarE.K. Lopez-KnowlesE. SriratanaA. GurungR. BagliettoL. GilesG.G. BaileyC.G. RaskoJ.E.J. ShieldsB.J. PriceJ.T. MajerusP.W. SutherlandR.L. TiganisT. McLeanC.A. MitchellC.A. Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers.Proc. Natl. Acad. Sci. USA201010751222312223610.1073/pnas.1015245107 21127264
     [Google Scholar]
  36. YuJ.S.L. CuiW. Proliferation, survival and metabolism: The role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination.Development2016143173050306010.1242/dev.137075 27578176
     [Google Scholar]
  37. BellacosaA. KumarC.C. CristofanoA.D. TestaJ.R. Activation of AKT kinases in cancer: Implications for therapeutic targeting.Adv. Cancer Res.2005942986
     [Google Scholar]
  38. HaoY. SamuelsY. LiQ. KrokowskiD. GuanB.J. WangC. JinZ. DongB. CaoB. FengX. XiangM. XuC. FinkS. MeropolN.J. XuY. ConlonR.A. MarkowitzS. KinzlerK.W. VelculescuV.E. BrunengraberH. WillisJ.E. LaFramboiseT. HatzoglouM. ZhangG.F. VogelsteinB. WangZ. Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer.Nat. Commun.2016711197110.1038/ncomms11971 27321283
     [Google Scholar]
  39. OgawaraY. KishishitaS. ObataT. IsazawaY. SuzukiT. TanakaK. MasuyamaN. GotohY. Akt enhances Mdm2-mediated ubiquitination and degradation of p53.J. Biol. Chem.200227724218432185010.1074/jbc.M109745200 11923280
     [Google Scholar]
  40. ArcaroA. GuerreiroA. The phosphoinositide 3-kinase pathway in human cancer: Genetic alterations and therapeutic implications.Curr. Genomics20078527130610.2174/138920207782446160 19384426
     [Google Scholar]
  41. RiquelmeI. TapiaO. EspinozaJ.A. LealP. BucheggerK. SandovalA. BizamaC. ArayaJ.C. PeekR.M. RoaJ.C. The gene expression status of the PI3K/AKT/mTOR pathway in gastric cancer tissues and cell lines.Pathol. Oncol. Res.201622479780510.1007/s12253‑016‑0066‑5 27156070
     [Google Scholar]
  42. XuF. NaL. LiY. ChenL. RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours.Cell Biosci.20201015410.1186/s13578‑020‑00416‑0 32266056
     [Google Scholar]
  43. VenkateshH.S. JohungT.B. CarettiV. NollA. TangY. NagarajaS. GibsonE.M. MountC.W. PolepalliJ. MitraS.S. WooP.J. MalenkaR.C. VogelH. BredelM. MallickP. MonjeM. Neuronal activity promotes glioma growth through Neuroligin-3 secretion.Cell2015161480381610.1016/j.cell.2015.04.012 25913192
     [Google Scholar]
  44. YuL. WeiJ. LiuP. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer.Semin. Cancer Biol.202285699410.1016/j.semcancer.2021.06.019 34175443
     [Google Scholar]
  45. HardyJ. Alzheimer’s disease: The amyloid cascade hypothesis: An update and reappraisal.J. Alzheimers Dis.20069s3Suppl.15115310.3233/JAD‑2006‑9S317 16914853
     [Google Scholar]
  46. DoT.D. EconomouN.J. ChamasA. BurattoS.K. SheaJ.E. BowersM.T. Interactions between amyloid-β and Tau fragments promote aberrant aggregates: Implications for amyloid toxicity.J. Phys. Chem. B201411838112201123010.1021/jp506258g 25153942
     [Google Scholar]
  47. LongH.Z. ChengY. ZhouZ.W. LuoH.Y. WenD.D. GaoL.C. PI3K/AKT Signal pathway: A target of natural products in the prevention and treatment of Alzheimer’s disease and Parkinson’s disease.Front. Pharmacol.20211264863610.3389/fphar.2021.648636 33935751
     [Google Scholar]
  48. MirdamadiY. BommhardtU. GoihlA. GuttekK. ZouboulisC.C. QuistS. GollnickH. Insulin and Insulin-like growth factor-1 can activate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in T cells in vitro.Dermatoendocrinol201791e135651810.1080/19381980.2017.1356518 29484090
     [Google Scholar]
  49. MatsuoF.S. AndradeM.F. LoyolaA.M. da SilvaS.J. SilvaM.J.B. CardosoS.V. de FariaP.R. Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients.Virchows Arch.2018472698399710.1007/s00428‑018‑2318‑0 29713826
     [Google Scholar]
  50. Yasuko KitagishiA.N. Yasunori Ogura, Satoru Matsuda Dietary regulation of PI3K/AKT/GSK-3β pathway in Alzheimer’s disease.Alzheimers Res. Ther.2014
     [Google Scholar]
  51. MatsudaS. NakagawaY. TsujiA. KitagishiY. NakanishiA. MuraiT. Implications of PI3K/AKT/PTEN signaling on superoxide dismutases expression and in the pathogenesis of Alzheimer’s disease.Diseases2018622810.3390/diseases6020028 29677102
     [Google Scholar]
  52. CuiW. WangS. WangZ. WangZ. SunC. ZhangY. Inhibition of PTEN attenuates endoplasmic reticulum stress and apoptosis via activation of PI3K/AKT pathway in Alzheimer’s disease.Neurochem. Res.201742113052306010.1007/s11064‑017‑2338‑1 28819903
     [Google Scholar]
  53. WongH.K.A. VeremeykoT. PatelN. LemereC.A. WalshD.M. EsauC. VanderburgC. KrichevskyA.M. De-repression of FOXO3a death axis by microRNA-132 and -212 causes neuronal apoptosis in Alzheimer’s disease.Hum. Mol. Genet.201322153077309210.1093/hmg/ddt164 23585551
     [Google Scholar]
  54. ZhangH. KongQ. WangJ. JiangY. HuaH. Complex roles of cAMP–PKA–CREB signaling in cancer.Exp. Hematol. Oncol.2020913210.1186/s40164‑020‑00191‑1 33292604
     [Google Scholar]
  55. FujishitaT. KojimaY. Kajino-SakamotoR. Mishiro-SatoE. ShimizuY. HosodaW. YamaguchiR. TaketoM.M. AokiM. The cAMP/PKA/CREB and TGFβ/SMAD4 pathways regulate stemness and metastatic potential in colorectal cancer cells.Cancer Res.202282224179419010.1158/0008‑5472.CAN‑22‑1369 36066360
     [Google Scholar]
  56. McKenzieA.J. CampbellS.L. HoweA.K. HoweA.K. Protein kinase A activity and anchoring are required for ovarian cancer cell migration and invasion.PLoS One2011610e2655210.1371/journal.pone.0026552 22028904
     [Google Scholar]
  57. JiangK. YaoG. HuL. YanY. LiuJ. ShiJ. ChangY. ZhangY. LiangD. ShenD. ZhangG. MengS. PiaoH. MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling.Cell Death Dis.202011423010.1038/s41419‑020‑2381‑8 32286266
     [Google Scholar]
  58. MoonE.Y. LeeG.H. LeeM.S. KimH.M. LeeJ.W. Phosphodiesterase inhibitors control A172 human glioblastoma cell death through cAMP-mediated activation of protein kinase A and Epac1/Rap1 pathways.Life Sci.2012909-1037338010.1016/j.lfs.2011.12.010 22227470
     [Google Scholar]
  59. CohenJ.R. ResnickD.Z. NiewiadomskiP. DongH. LiauL.M. WaschekJ.A. Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures.BMC Cancer201010167610.1186/1471‑2407‑10‑676 21143927
     [Google Scholar]
  60. AmidfarM. de OliveiraJ. KucharskaE. BudniJ. KimY.K. The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease.Life Sci.202025711802010.1016/j.lfs.2020.118020 32603820
     [Google Scholar]
  61. RammsD.J. RaimondiF. ArangN. HerbergF.W. TaylorS.S. GutkindJ.S. SchulteG. Gαs–Protein KinaseA. G α s–Protein Kinase A (PKA) pathway signalopathies: The emerging genetic landscape and therapeutic potential of human diseases driven by Aberrant G α s-PKA signaling.Pharmacol. Rev.20217341326136810.1124/pharmrev.120.000269
     [Google Scholar]
  62. ChenY. HuangX. ZhangY. RockensteinE. BuG. GoldeT.E. MasliahE. XuH. Alzheimer’s β-Secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-Amyloid.J. Neurosci.20123233113901139510.1523/JNEUROSCI.0757‑12.2012 22895721
     [Google Scholar]
  63. PugazhenthiS. WangM. PhamS. SzeC.I. EckmanC.B. Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons.Mol. Neurodegener.2011616010.1186/1750‑1326‑6‑60 21854604
     [Google Scholar]
  64. LiA. YiM. QinS. SongY. ChuQ. WuK. Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy.J. Hematol. Oncol.20191213510.1186/s13045‑019‑0721‑x 30935414
     [Google Scholar]
  65. XiaT. KonnoH. AhnJ. BarberG.N. Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with Tumorigenesis.Cell Rep.201614228229710.1016/j.celrep.2015.12.029 26748708
     [Google Scholar]
  66. XiaT. KonnoH. BarberG.N. Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis.Cancer Res.201676226747675910.1158/0008‑5472.CAN‑16‑1404 27680683
     [Google Scholar]
  67. KitajimaS. IvanovaE. GuoS. YoshidaR. CampisiM. SundararamanS.K. TangeS. MitsuishiY. ThaiT.C. MasudaS. PielB.P. ShollL.M. KirschmeierP.T. PaweletzC.P. WatanabeH. YajimaM. BarbieD.A. Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer.Cancer Discov.201991344510.1158/2159‑8290.CD‑18‑0689 30297358
     [Google Scholar]
  68. JiangM. ChenP. WangL. LiW. ChenB. LiuY. WangH. ZhaoS. YeL. HeY. ZhouC. cGAS-STING, an important pathway in cancer immunotherapy.J. Hematol. Oncol.20201318110.1186/s13045‑020‑00916‑z 32571374
     [Google Scholar]
  69. BergerG. MarloyeM. LawlerS.E. Pharmacological modulation of the sting pathway for cancer immunotherapy.Trends Mol. Med.201925541242710.1016/j.molmed.2019.02.007 30885429
     [Google Scholar]
  70. DouZ. GhoshK. VizioliM.G. ZhuJ. SenP. WangensteenK.J. SimithyJ. LanY. LinY. ZhouZ. CapellB.C. XuC. XuM. KieckhaeferJ.E. JiangT. Shoshkes-CarmelM. TanimK.M.A.A. BarberG.N. SeykoraJ.T. MillarS.E. KaestnerK.H. GarciaB.A. AdamsP.D. BergerS.L. Cytoplasmic chromatin triggers inflammation in senescence and cancer.Nature2017550767640240610.1038/nature24050 28976970
     [Google Scholar]
  71. JingW. McAllisterD. VonderhaarE.P. PalenK. RieseM.J. GershanJ. JohnsonB.D. DwinellM.B. STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models.J. Immunother. Cancer20197111510.1186/s40425‑019‑0573‑5 31036082
     [Google Scholar]
  72. WooS.R. FuertesM.B. CorralesL. SprangerS. FurdynaM.J. LeungM.Y.K. DugganR. WangY. BarberG.N. FitzgeraldK.A. AlegreM.L. GajewskiT.F. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.Immunity201441583084210.1016/j.immuni.2014.10.017 25517615
     [Google Scholar]
  73. YangH. LeeW.S. KongS.J. KimC.G. KimJ.H. ChangS.K. KimS. KimG. ChonH.J. KimC. STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade.J. Clin. Invest.2019129104350436410.1172/JCI125413 31343989
     [Google Scholar]
  74. JinM. ShiwakuH. TanakaH. ObitaT. OhuchiS. YoshiokaY. JinX. KondoK. FujitaK. HommaH. NakajimaK. MizuguchiM. OkazawaH. Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation.Nat. Commun.2021121656510.1038/s41467‑021‑26851‑2 34782623
     [Google Scholar]
  75. PaulB.D. SnyderS.H. BohrV.A. Signaling by cGAS–STING in neurodegeneration, neuroinflammation, and aging.Trends Neurosci.2021442839610.1016/j.tins.2020.10.008 33187730
     [Google Scholar]
  76. XieX. MaG. LiX. ZhaoJ. ZhaoZ. ZengJ. Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice.Nature. Aging20233220221210.1038/s43587‑022‑00337‑2 37118112
     [Google Scholar]
  77. HouY. WeiY. LautrupS. YangB. WangY. CordonnierS. MattsonM.P. CroteauD.L. BohrV.A. NAD + supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS–STING.Proc. Natl. Acad. Sci. USA202111837e201122611810.1073/pnas.2011226118 34497121
     [Google Scholar]
  78. BalkwillF. MantovaniA. Inflammation and cancer: Back to Virchow?Lancet2001357925553954510.1016/S0140‑6736(00)04046‑0 11229684
     [Google Scholar]
  79. SunE. MotolaniA. CamposL. LuT. The pivotal role of NF-kB in the pathogenesis and therapeutics of Alzheimer’s disease.Int. J. Mol. Sci.20222316897210.3390/ijms23168972 36012242
     [Google Scholar]
  80. BonizziG. KarinM. The two NF-κB activation pathways and their role in innate and adaptive immunity.Trends Immunol.200425628028810.1016/j.it.2004.03.008 15145317
     [Google Scholar]
  81. RasmiR.R. SakthivelK.M. GuruvayoorappanC. NF-κB inhibitors in treatment and prevention of lung cancer.Biomed. Pharmacother.202013011056910.1016/j.biopha.2020.110569 32750649
     [Google Scholar]
  82. KhongthongP. RoseweirA.K. EdwardsJ. The NF-KB pathway and endocrine therapy resistance in breast cancer.Endocr. Relat. Cancer2019266R369R38010.1530/ERC‑19‑0087 32013374
     [Google Scholar]
  83. KarinM. Nuclear factor-κB in cancer development and progression.Nature2006441709243143610.1038/nature04870 16724054
     [Google Scholar]
  84. KarinM. LinA. NF-κB at the crossroads of life and death.Nat. Immunol.20023322122710.1038/ni0302‑221 11875461
     [Google Scholar]
  85. KarinM. CaoY. GretenF.R. LiZ.W. NF-κB in cancer: From innocent bystander to major culprit.Nat. Rev. Cancer20022430131010.1038/nrc780 12001991
     [Google Scholar]
  86. GrivennikovS.I. KarinM. Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer.Cytokine Growth Factor Rev.2010211111910.1016/j.cytogfr.2009.11.005 20018552
     [Google Scholar]
  87. WebsterG.A. PerkinsN.D. Transcriptional cross talk between NF-κB and p53.Mol. Cell. Biol.19991953485349510.1128/MCB.19.5.3485 10207072
     [Google Scholar]
  88. LengF. EdisonP. Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?Nat. Rev. Neurol.202117315717210.1038/s41582‑020‑00435‑y 33318676
     [Google Scholar]
  89. ShihR.H. WangC.Y. YangC.M. NF-kappaB signaling pathways in neurological inflammation: A mini review.Front. Mol. Neurosci.201587710.3389/fnmol.2015.00077 26733801
     [Google Scholar]
  90. ChenC.H. ZhouW. LiuS. DengY. CaiF. ToneM. ToneY. TongY. SongW. Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease.Int. J. Neuropsychopharmacol.2012151779010.1017/S1461145711000149 21329555
     [Google Scholar]
  91. ThawkarB.S. KaurG. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease.J. Neuroimmunol.2019326627410.1016/j.jneuroim.2018.11.010 30502599
     [Google Scholar]
  92. González-ReyesR.E. Nava-MesaM.O. Vargas-SánchezK. Ariza-SalamancaD. Mora-MuñozL. Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective.Front. Mol. Neurosci.20171042710.3389/fnmol.2017.00427 29311817
     [Google Scholar]
  93. FengY. LiX. ZhouW. LouD. HuangD. LiY. KangY. XiangY. LiT. ZhouW. SongW. Regulation of SET gene expression by NFkB.Mol. Neurobiol.20175464477448510.1007/s12035‑016‑9967‑2 27351675
     [Google Scholar]
  94. LaneD. LevineA. p53 Research: The past thirty years and the next thirty years.Cold Spring Harb. Perspect. Biol.2010212a00089310.1101/cshperspect.a000893 20463001
     [Google Scholar]
  95. HassinO. OrenM. Drugging p53 in cancer: One protein, many targets.Nat. Rev. Drug Discov.202322212714410.1038/s41573‑022‑00571‑8 36216888
     [Google Scholar]
  96. SeoJ. ParkM. Molecular crosstalk between cancer and neurodegenerative diseases.Cell. Mol. Life Sci.202077142659268010.1007/s00018‑019‑03428‑3 31884567
     [Google Scholar]
  97. XuZ. WuW. YanH. HuY. HeQ. LuoP. Regulation of p53 stability as a therapeutic strategy for cancer.Biochem. Pharmacol.202118511440710.1016/j.bcp.2021.114407 33421376
     [Google Scholar]
  98. BlandinoG. Di AgostinoS. New therapeutic strategies to treat human cancers expressing mutant p53 proteins.J. Exp. Clin. Cancer Res.20183713010.1186/s13046‑018‑0705‑7 29448954
     [Google Scholar]
  99. XiongY. ZhangY. XiongS. Williams-VillaloboA.E. A Glance of p53 functions in brain development, neural stem cells, and brain cancer.Biology20209928510.3390/biology9090285 32932978
     [Google Scholar]
  100. TanakaN. ZhaoM. TangL. PatelA.A. XiQ. VanH.T. TakahashiH. OsmanA.A. ZhangJ. WangJ. MyersJ.N. ZhouG. Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cells by targeting the transcription factors FOXO3a and FOXM1.Oncogene201837101279129210.1038/s41388‑017‑0032‑z 29269868
     [Google Scholar]
  101. ChoiH.J. JheY.L. KimJ. LimJ.Y. LeeJ.E. ShinM.K. CheongJ.H. FoxM1-dependent and fatty acid oxidation-mediated ROS modulation is a cell-intrinsic drug resistance mechanism in cancer stem-like cells.Redox Biol.20203610158910.1016/j.redox.2020.101589 32521504
     [Google Scholar]
  102. ZabłockaA. KazanaW. SochockaM. StańczykiewiczB. JanuszM. LeszekJ. OrzechowskaB. Inverse correlation between Alzheimer’s disease and cancer: Short overview.Mol. Neurobiol.202158126335634910.1007/s12035‑021‑02544‑1 34523079
     [Google Scholar]
  103. Wassim ChatooM.A. p53 Pro-oxidant activity in the central nervous system: Implication in aging and neurodegenerative diseases.Antioxid. Redox Signal.20111561729173710.1089/ars.2010.3610 20849375
     [Google Scholar]
  104. HooperC. MeimaridouE. TavassoliM. MelinoG. LovestoneS. KillickR. p53 is upregulated in Alzheimer’s disease and induces tau phosphorylation in HEK293a cells.Neurosci. Lett.20074181343710.1016/j.neulet.2007.03.026 17399897
     [Google Scholar]
  105. ClarkJ.S. KayedR. AbateG. UbertiD. KinnonP. PiccirellaS. Post-translational modifications of the p53 protein and the impact in Alzheimer’s disease: A Review of the literature.Front. Aging Neurosci.20221483528810.3389/fnagi.2022.835288 35572126
     [Google Scholar]
  106. SewardM.E. SwansonE. NorambuenaA. ReimannA. CochranJ.N. LiR. RobersonE.D. BloomG.S. Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer’s disease.J. Cell Sci.201312651278128610.1242/jcs.1125880 23345405
     [Google Scholar]
  107. MajdS. PowerJ. MajdZ. Alzheimer’s disease and cancer: When two monsters cannot be together.Front. Neurosci.20191315510.3389/fnins.2019.00155 30881282
     [Google Scholar]
  108. UbertiD. LanniC. CarsanaT. FrancisconiS. MissaleC. RacchiM. GovoniS. MemoM. Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer’s disease patients.Neurobiol. Aging20062791193120110.1016/j.neurobiolaging.2005.06.013 16165254
     [Google Scholar]
  109. LanniC. RacchiM. StangaS. MazziniG. RanzenigoA. PolottiR. MemoM. GovoniS. UbertiD. Unfolded p53 in blood as a predictive signature signature of the transition from mild cognitive impairment to Alzheimer’s disease.J. Alzheimers Dis.20102019710410.3233/JAD‑2010‑1347 20164600
     [Google Scholar]
  110. BuizzaL. CeniniG. LanniC. Ferrari-ToninelliG. PrandelliC. GovoniS. BuosoE. RacchiM. BarcikowskaM. StyczynskaM. SzybinskaA. ButterfieldD.A. MemoM. UbertiD. UbertiD. Conformational altered p53 as an early marker of oxidative stress in Alzheimer’s disease.PLoS One201271e2978910.1371/journal.pone.0029789 22242180
     [Google Scholar]
  111. PuW. ZhengY. PengY. Prolyl isomerase Pin1 in human cancer: Function, mechanism, and significance.Front. Cell Dev. Biol.2020816810.3389/fcell.2020.00168 32296699
     [Google Scholar]
  112. ZhuZ. ZhangH. LangF. LiuG. GaoD. LiB. LiuY. Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/β-catenin signaling.Clin. Transl. Oncol.201618879279710.1007/s12094‑015‑1431‑7 26497355
     [Google Scholar]
  113. RustighiA. ZanniniA. TiberiL. SommaggioR. PiazzaS. SorrentinoG. NuzzoS. TuscanoA. EternoV. BenvenutiF. SantarpiaL. AifantisI. RosatoA. BicciatoS. ZambelliA. Del SalG. Prolyl‐isomerase Pin1 controls normal and cancer stem cells of the breast.EMBO Mol. Med.2014619911910.1002/emmm.201302909 24357640
     [Google Scholar]
  114. NakatsuY. YamamotoyaT. UedaK. OnoH. InoueM.K. MatsunagaY. KushiyamaA. SakodaH. FujishiroM. MatsubaraA. AsanoT. Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells.Cancer Lett.202047010611410.1016/j.canlet.2019.10.043 31678165
     [Google Scholar]
  115. ChuangH.H. ZhenY.Y. TsaiY.C. ChuangC.H. HuangM.S. HsiaoM. YangC.J. Targeting Pin1 for modulation of cell motility and cancer therapy.Biomedicines20219435910.3390/biomedicines9040359 33807199
     [Google Scholar]
  116. WangJ. ZhangN. HanQ. LuW. WangL. YangD. ZhengM. ZhangZ. LiuH. LeeT.H. ZhouX.Z. LuK.P. Pin1 inhibition reverses the acquired resistance of human hepatocellular carcinoma cells to Regorafenib via the Gli1/Snail/E-cadherin pathway.Cancer Lett.2019444829310.1016/j.canlet.2018.12.010 30583078
     [Google Scholar]
  117. RyoA. HiraiA. NishiM. LiouY.C. PerremK. LinS.C. HiranoH. LeeS.W. AokiI. A suppressive role of the prolyl isomerase Pin1 in cellular apoptosis mediated by the death-associated protein Daxx.J. Biol. Chem.200728250366713668110.1074/jbc.M704145200 17938171
     [Google Scholar]
  118. YangW. ZhengY. XiaY. JiH. ChenX. GuoF. LyssiotisC.A. AldapeK. CantleyL.C. LuZ. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect.Nat. Cell Biol.201214121295130410.1038/ncb2629 23178880
     [Google Scholar]
  119. ChengC.W. TseE. PIN1 in cell cycle control and cancer.Front. Pharmacol.20189136710.3389/fphar.2018.01367 30534074
     [Google Scholar]
  120. YuJ.H. Im, C.Y.; Min, S.H. Function of PIN1 in cancer development and its inhibitors as cancer therapeutics.Front. Cell Dev. Biol.2020812010.3389/fcell.2020.00120 32258027
     [Google Scholar]
  121. JeongK. KimS.J. OhY. KimH. LeeY.S. KwonB.S. ParkS. ParkK.C. YoonK.S. KimS.S. HaJ. KangI. ChoeW. p53 negatively regulates Pin1 expression under ER stress.Biochem. Biophys. Res. Commun.2014454451852310.1016/j.bbrc.2014.10.101 25451271
     [Google Scholar]
  122. LuP.J. WulfG. ZhouX.Z. DaviesP. LuK.P. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein.Nature1999399673878478810.1038/21650
     [Google Scholar]
  123. LimJ. BalastikM. LeeT.H. NakamuraK. LiouY.C. SunA. FinnG. PastorinoL. LeeV.M.Y. LuK.P. Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy.J. Clin. Invest.200811851877188910.1172/JCI34308 18431510
     [Google Scholar]
  124. PastorinoL. SunA. LuP.J. ZhouX.Z. BalastikM. FinnG. WulfG. LimJ. LiS.H. LiX. XiaW. NicholsonL.K. LuK.P. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production.Nature2006440708352853410.1038/nature04543 16554819
     [Google Scholar]
  125. NakamuraK. GreenwoodA. BinderL. BigioE.H. DenialS. NicholsonL. ZhouX.Z. LuK.P. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer’s disease.Cell2012149123224410.1016/j.cell.2012.02.016 22464332
     [Google Scholar]
  126. MalterJ.S. Pin1 and Alzheimer’s disease.Transl. Res.2022 36162703
     [Google Scholar]
  127. WangZ. ZhaoT. ZhangS. WangJ. ChenY. ZhaoH. YangY. ShiS. ChenQ. LiuK. The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy.Biomark. Res.2021916810.1186/s40364‑021‑00323‑7 34488905
     [Google Scholar]
  128. LiuY. QiX. DonnellyL. Elghobashi-MeinhardtN. LongT. ZhouR.W. SunY. WangB. LiX. Mechanisms and inhibition of Porcupine-mediated Wnt acylation.Nature2022607792081682210.1038/s41586‑022‑04952‑2 35831507
     [Google Scholar]
  129. ShiraiF. MizutaniA. YashirodaY. TsumuraT. KanoY. MuramatsuY. ChikadaT. YukiH. NiwaH. SatoS. WashizukaK. KodaY. MazakiY. JangM.K. YoshidaH. NagamoriA. OkueM. WatanabeT. KitamuraK. ShitaraE. HonmaT. UmeharaT. ShirouzuM. FukamiT. SeimiyaH. YoshidaM. KoyamaH. Design and discovery of an orally efficacious spiroindolinone-based tankyrase inhibitor for the treatment of colon cancer.J. Med. Chem.20206384183420410.1021/acs.jmedchem.0c00045 32202790
     [Google Scholar]
  130. HuangS.M.A. MishinaY.M. LiuS. CheungA. StegmeierF. MichaudG.A. CharlatO. WielletteE. ZhangY. WiessnerS. HildM. ShiX. WilsonC.J. MickaninC. MyerV. FazalA. TomlinsonR. SerlucaF. ShaoW. ChengH. ShultzM. RauC. SchirleM. SchleglJ. GhidelliS. FawellS. LuC. CurtisD. KirschnerM.W. LengauerC. FinanP.M. TallaricoJ.A. BouwmeesterT. PorterJ.A. BauerA. CongF. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.Nature2009461726461462010.1038/nature08356 19759537
     [Google Scholar]
  131. WangJ. CaiH. LiuQ. XiaY. XingL. ZuoQ. ZhangY. ChenC. XuK. YinP. ChenT. Cinobufacini inhibits colon cancer invasion and metastasis via suppressing Wnt/β-Catenin signaling pathway and EMT.Am. J. Chin. Med.202048370371810.1142/S0192415X20500354 32329642
     [Google Scholar]
  132. MarkhamA. Idelalisib: First global approval.Drugs201474141701170710.1007/s40265‑014‑0285‑6 25187123
     [Google Scholar]
  133. KumarA. BhatiaR. ChawlaP. AnghoreD. SainiV. RawalR.K. Copanlisib: Novel PI3K inhibitor for the treatment of Lymphoma.Anticancer. Agents Med. Chem.202020101158117210.2174/1871520620666200317105207 32183683
     [Google Scholar]
  134. AlzahraniA.S. PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside.Semin. Cancer Biol.20195912513210.1016/j.semcancer.2019.07.009 31323288
     [Google Scholar]
  135. LucchiS. CalebiroD. de FilippisT. GrassiE.S. BorghiM.O. PersaniL. 8-Chloro-cyclic AMP and protein kinase A I-selective cyclic AMP analogs inhibit cancer cell growth through different mechanisms.PLoS One201166e2078510.1371/journal.pone.0020785 21695205
     [Google Scholar]
  136. ChoiK.Y. AhnY.H. AhnH.W. ChoY.J. HongS.H. Involvement of Akt2/protein kinase B β (PKBβ) in the 8‐Cl‐cAMP‐induced cancer cell growth inhibition.J. Cell. Physiol.2013228489090210.1002/jcp.24240 23018889
     [Google Scholar]
  137. IllianoM. ConteM. SalzilloA. RagoneA. SpinaA. NebbiosoA. AltucciL. SapioL. NaviglioS. The KDM inhibitor GSKJ4 triggers CREB downregulation via a protein kinase A and Proteasome-dependent mechanism in human acute Myeloid Leukemia cells.Front. Oncol.20201079910.3389/fonc.2020.00799 32582541
     [Google Scholar]
  138. FrancicaB.J. GhasemzadehA. DesbienA.L. TheodrosD. SivickK.E. ReinerG.L. Hix GlickmanL. MarciscanoA.E. SharabiA.B. LeongM.L. McWhirterS.M. DubenskyT.W.Jr PardollD.M. DrakeC.G. TNFα and radioresistant stromal cells are essential for therapeutic efficacy of cyclic Dinucleotide STING agonists in nonimmunogenic tumors.Cancer Immunol. Res.20186442243310.1158/2326‑6066.CIR‑17‑0263 29472271
     [Google Scholar]
  139. Meric-BernstamF. SweisR.F. HodiF.S. MessersmithW.A. AndtbackaR.H.I. InghamM. LewisN. ChenX. PelletierM. ChenX. WuJ. DubenskyT.W. McWhirterS.M. MüllerT. NairN. LukeJ.J. PhaseI. PhaseI. Dose-Escalation trial of MIW815 (ADU-S100), an Intratumoral STING agonist, in patients with advanced/metastatic solid tumors or Lymphomas.Clin. Cancer Res.202228467768810.1158/1078‑0432.CCR‑21‑1963 34716197
     [Google Scholar]
  140. ZandbergD.P. FerrisR. LauxD. MehraR. NabellL. KaczmarJ. GibsonM.K. KimY.J. NeupaneP. BaumanJ. JulianR. AdkinsD. CohenE. BurtnessB. BerminghamC. DupageA. DesbienA. LoiA. NuytenD.S.A. SabaN.F. 71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results.Ann. Oncol.202031S1446S144710.1016/j.annonc.2020.10.559
     [Google Scholar]
  141. ChangW. AltmanM.D. LesburgC.A. PereraS.A. PiesvauxJ.A. SchroederG.K. WyssD.F. CemerskiS. ChenY. DiNunzioE. HaidleA.M. HoT. KarivI. KnemeyerI. KopinjaJ.E. LaceyB.M. LaskeyJ. LimJ. LongB.J. MaY. MaddessM.L. PanB.S. PreslandJ.P. SpoonerE. SteinhuebelD. TruongQ. ZhangZ. FuJ. AddonaG.H. NorthrupA.B. ParmeeE. TataJ.R. BennettD.J. CummingJ.N. SiuT. TrotterB.W. Discovery of MK-1454: A potent cyclic dinucleotide stimulator of interferon genes agonist for the treatment of cancer.J. Med. Chem.20226575675568910.1021/acs.jmedchem.1c02197 35332774
     [Google Scholar]
  142. HarringtonK.J. BrodyJ. InghamM. StraussJ. CemerskiS. WangM. TseA. KhilnaniA. MarabelleA. GolanT. Preliminary results of the first-in-human (FIH) study of MK-1454, an agonist of stimulator of interferon genes (STING), as monotherapy or in combination with pembrolizumab (pembro) in patients with advanced solid tumors or lymphomas.Ann. Oncol.201829viii71210.1093/annonc/mdy424.015
     [Google Scholar]
  143. ConlonJ. BurdetteD.L. SharmaS. BhatN. ThompsonM. JiangZ. RathinamV.A.K. MonksB. JinT. XiaoT.S. VogelS.N. VanceR.E. FitzgeraldK.A. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid.J. Immunol.2013190105216522510.4049/jimmunol.1300097 23585680
     [Google Scholar]
  144. RamanjuluJ.M. PesiridisG.S. YangJ. ConchaN. SinghausR. ZhangS.Y. TranJ.L. MooreP. LehmannS. EberlH.C. MuelbaierM. SchneckJ.L. ClemensJ. AdamM. MehlmannJ. RomanoJ. MoralesA. KangJ. LeisterL. GraybillT.L. CharnleyA.K. YeG. NevinsN. BehniaK. WolfA.I. KasparcovaV. NurseK. WangL. PuhlA.C. LiY. KleinM. HopsonC.B. GussJ. BantscheffM. BergaminiG. ReillyM.A. LianY. DuffyK.J. AdamsJ. FoleyK.P. GoughP.J. MarquisR.W. SmothersJ. HoosA. BertinJ. Design of amidobenzimidazole STING receptor agonists with systemic activity.Nature2018564773643944310.1038/s41586‑018‑0705‑y 30405246
     [Google Scholar]
  145. PanB.S. PereraS.A. PiesvauxJ.A. PreslandJ.P. SchroederG.K. CummingJ.N. TrotterB.W. AltmanM.D. BuevichA.V. CashB. CemerskiS. ChangW. ChenY. DandlikerP.J. FengG. HaidleA. HendersonT. JewellJ. KarivI. KnemeyerI. KopinjaJ. LaceyB.M. LaskeyJ. LesburgC.A. LiangR. LongB.J. LuM. MaY. MinnihanE.C. O’DonnellG. OtteR. PriceL. RakhilinaL. SauvagnatB. SharmaS. TyagarajanS. WooH. WyssD.F. XuS. BennettD.J. AddonaG.H. An orally available non-nucleotide STING agonist with antitumor activity.Science20203696506eaba609810.1126/science.aba6098 32820094
     [Google Scholar]
  146. WangW.H. HuangJ.Q. ZhengG.F. LamS.K. KarlbergJ. WongB.C. Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: A systematic review and meta-analysis.J. Natl. Cancer Inst.200395231784179110.1093/jnci/djg106 14652240
     [Google Scholar]
  147. YuH. LinL. ZhangZ. ZhangH. HuH. Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study.Signal Transduct. Target. Ther.20205120910.1038/s41392‑020‑00312‑6
     [Google Scholar]
  148. HoeselB. SchmidJ.A. The complexity of NF-κB signaling in inflammation and cancer.Mol. Cancer20131218610.1186/1476‑4598‑12‑86 23915189
     [Google Scholar]
  149. DermawanJ.K.T. GurovaK. PinkJ. DowlatiA. DeS. NarlaG. SharmaN. StarkG.R. Quinacrine overcomes resistance to erlotinib by inhibiting FACT, NF-κB, and cell-cycle progression in non-small cell lung cancer.Mol. Cancer Ther.20141392203221410.1158/1535‑7163.MCT‑14‑0013 25028470
     [Google Scholar]
  150. GaptulbarovaK.A. TsyganovM.M. PevznerA.M. IbragimovaM.K. LitviakovN.V. NF-kB as a potential prognostic marker and a candidate for targeted therapy of cancer.Exp. Oncol.202342426326910.32471/exp‑oncology.2312‑8852.vol‑42‑no‑4.15414 33355866
     [Google Scholar]
  151. TomitaM. WrightJ. KelloggR. ParisotN. ClarkM. LiX. DaviesM. KashalaA. TrehuE. MurrenJ. P-798 Phase I study of topotecan and bortezomib (Vc) withpharmacokinetic and pharmacodynamic correlates.Lung Cancer200549S32910.1016/S0169‑5002(05)81291‑7
     [Google Scholar]
  152. ArnoldS.M. ChanskyK. LeggasM. ThompsonM.A. VillanoJ.L. HammJ. SanbornR.E. WeissG.J. ChattaG. BaggstromM.Q. Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553).Invest. New Drugs201735560861510.1007/s10637‑017‑0441‑4 28204981
     [Google Scholar]
  153. VaisittiT. GaudinoF. OukS. MoscvinM. VitaleN. SerraS. ArrugaF. ZakrzewskiJ.L. LiouH.C. AllanJ.N. FurmanR.R. DeaglioS. Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor.Haematologica2017102111878188910.3324/haematol.2017.173419 28860341
     [Google Scholar]
  154. YuM. QiB. XiaoxiangW. XuJ. LiuX. Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-κB pathway.Biomed. Pharmacother.20179067768510.1016/j.biopha.2017.04.001 28415048
     [Google Scholar]
  155. PengZ. Current status of gendicine in China: Recombinant human Ad-p53 agent for treatment of cancers.Hum. Gene Ther.20051691016102710.1089/hum.2005.16.1016 16149900
     [Google Scholar]
  156. BirsenR. LarrueC. DecroocqJ. JohnsonN. GuiraudN. GotanegreM. Cantero-AguilarL. GrignanoE. HuynhT. FontenayM. KosmiderO. MayeuxP. ChapuisN. SarryJ.E. TamburiniJ. BouscaryD. APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.Haematologica2021107240341610.3324/haematol.2020.259531 33406814
     [Google Scholar]
  157. MaslahN. SalomaoN. DrevonL. VergerE. PartoucheN. LyP. AubinP. NaouiN. SchlageterM.H. BallyC. MiekoutimaE. RahméR. Lehmann-CheJ. AdesL. FenauxP. CassinatB. GiraudierS. Synergistic effects of PRIMA-1 Met (APR-246) and 5-azacitidine in TP53 -mutated myelodysplastic syndromes and acute myeloid leukemia.Haematologica202010561539155110.3324/haematol.2019.218453 31488557
     [Google Scholar]
  158. NishikawaS. IwakumaT. Drugs targeting p53 mutations with FDA approval and in clinical trials.Cancers202315242910.3390/cancers15020429 36672377
     [Google Scholar]
  159. CampanerE. RustighiA. ZanniniA. CristianiA. PiazzaS. CianiY. KalidO. GolanG. BalogluE. ShachamS. ValsasinaB. CucchiU. PippioneA.C. LolliM.L. GiabbaiB. StoriciP. CarloniP. RossettiG. BenvenutiF. BelloE. D’IncalciM. CappuzzelloE. RosatoA. Del SalG. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action.Nat. Commun.2017811577210.1038/ncomms15772 28598431
     [Google Scholar]
  160. DubiellaC. PinchB.J. KoikawaK. ZaidmanD. PoonE. ManzT.D. NabetB. HeS. ResnickE. RogelA. LangerE.M. DanielC.J. SeoH.S. ChenY. AdelmantG. SharifzadehS. FicarroS.B. JaminY. Martins da CostaB. ZimmermanM.W. LianX. KibeS. KozonoS. DoctorZ.M. BrowneC.M. YangA. Stoler-BarakL. ShahR.B. VangosN.E. GeffkenE.A. OrenR. KoideE. SidiS. ShulmanZ. WangC. MartoJ.A. Dhe-PaganonS. LookT. ZhouX.Z. LuK.P. SearsR.C. CheslerL. GrayN.S. LondonN. Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.Nat. Chem. Biol.202117995496310.1038/s41589‑021‑00786‑7 33972797
     [Google Scholar]
  161. KozonoS. LinY.M. SeoH.S. PinchB. LianX. QiuC. HerbertM.K. ChenC.H. TanL. GaoZ.J. MassefskiW. DoctorZ.M. JacksonB.P. ChenY. Dhe-PaganonS. LuK.P. ZhouX.Z. Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells.Nat. Commun.201891306910.1038/s41467‑018‑05402‑2 30093655
     [Google Scholar]
  162. LiangC. QiaoG. LiuY. TianL. HuiN. LiJ. MaY. LiH. ZhaoQ. CaoW. LiuH. RenX. Overview of all-trans-retinoic acid (ATRA) and its analogues: Structures, activities, and mechanisms in acute promyelocytic leukaemia.Eur. J. Med. Chem.202122011345110.1016/j.ejmech.2021.113451 33895500
     [Google Scholar]
  163. FinkH.A. LinskensE.J. MacDonaldR. SilvermanP.C. McCartenJ.R. TalleyK.M.C. ForteM.L. DesaiP.J. NelsonV.A. MillerM.A. HemmyL.S. BrasureM. TaylorB.C. NgW. OuelletteJ.M. SheetsK.M. WiltT.J. ButlerM. Benefits and harms of prescription drugs and supplements for treatment of clinical alzheimer-type dementia.Ann. Intern. Med.20201721065666810.7326/M19‑3887 32340037
     [Google Scholar]
  164. DingM.R. QuY.J. HuB. AnH.M. Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine.Biomed. Pharmacother.202215211320810.1016/j.biopha.2022.113208 35660246
     [Google Scholar]
  165. TiwariS.K. AgarwalS. SethB. YadavA. NairS. BhatnagarP. KarmakarM. KumariM. ChauhanL.K.S. PatelD.K. SrivastavaV. SinghD. GuptaS.K. TripathiA. ChaturvediR.K. GuptaK.C. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway.ACS Nano2014817610310.1021/nn405077y 24467380
     [Google Scholar]
  166. Varela-NallarL. ArredondoS.B. Tapia-RojasC. HanckeJ. InestrosaN.C. Andrographolide stimulates neurogenesis in the adult Hippocampus.Neural Plast.2015201511310.1155/2015/935403 26798521
     [Google Scholar]
  167. CisternasP. ZolezziJ.M. MartinezM. TorresV.I. WongG.W. InestrosaN.C. Wnt‐induced activation of glucose metabolism mediates the in vivo neuroprotective roles of Wnt signaling in Alzheimer disease.J. Neurochem.20191491547210.1111/jnc.14608 30300917
     [Google Scholar]
  168. YaoY. GaoZ. LiangW. KongL. JiaoY. LiS. TaoZ. YanY. YangJ. Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer’s disease model.Toxicol. Appl. Pharmacol.2015289347448110.1016/j.taap.2015.10.013 26525509
     [Google Scholar]
  169. LiuX. WangK. WeiX. XieT. LvB. ZhouQ. WangX. Interaction of NF-κB and Wnt/β-catenin signaling pathways in Alzheimer’s disease and potential active drug treatments.Neurochem. Res.202146471173110.1007/s11064‑021‑03227‑y 33523396
     [Google Scholar]
  170. QinG WangY LiuZ ManaL HuangS WangP Shenzhiling oral solution promotes myelin repair through PI3K/Akt-mTOR pathway in STZ-induced SAD mice.3 Biotech2021117361
     [Google Scholar]
  171. ZhengM. LiuZ. ManaL. QinG. HuangS. GongZ. TianM. HeY. WangP. Shenzhiling oral liquid protects the myelin sheath against Alzheimer’s disease through the PI3K/Akt-mTOR pathway.J. Ethnopharmacol.202127811426410.1016/j.jep.2021.114264 34082015
     [Google Scholar]
  172. ZhangD. WangZ. ShengC. PengW. HuiS. GongW. ChenS. Icariin prevents amyloid beta-induced apoptosis via the PI3K/Akt pathway in PC-12 cells.Evid. Based Complement. Alternat. Med.201520151910.1155/2015/235265 25705234
     [Google Scholar]
  173. YangW. LiuY. XuQ-Q. XianY-F. LinZ-X. Sulforaphene Ameliorates neuroinflammation and hyperphosphorylated tau protein via regulating the pi3k/akt/gsk-3βpathway in experimental models of Alzheimer’s disease.Oxid. Med. Cell. Longev.2020202011710.1155/2020/8825387
     [Google Scholar]
  174. ZhangY. ZhangZ. WangH. CaiN. ZhouS. ZhaoY. ChenX. ZhengS. SiQ. ZhangW. Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3K/AKT/GSK-3β pathway.Mol. Med. Rep.20161432778278410.3892/mmr.2016.5556 27485139
     [Google Scholar]
  175. SongX.Y. HuJ.F. ChuS.F. ZhangZ. XuS. YuanY.H. HanN. LiuY. NiuF. HeX. ChenN.H. Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats.Eur. J. Pharmacol.20137101-3293810.1016/j.ejphar.2013.03.051 23588117
     [Google Scholar]
  176. ShiY.Q. HuangT.W. ChenL.M. PanX.D. ZhangJ. ZhuY.G. ChenX.C. Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice.J. Alzheimers Dis.201019397798910.3233/JAD‑2010‑1296 20157253
     [Google Scholar]
  177. TchantchouF. XuY. WuY. ChristenY. LuoY. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease.FASEB J.200721102400240810.1096/fj.06‑7649com 17356006
     [Google Scholar]
  178. SandersO. RajagopalL. Phosphodiesterase inhibitors for Alzheimer’s disease: A systematic review of clinical trials and epidemiology with a mechanistic rationale.J. Alzheimers Dis. Rep.20204118521510.3233/ADR‑200191 32715279
     [Google Scholar]
  179. LiQ.Q. ShiG.X. YangJ.W. LiZ.X. ZhangZ.H. HeT. WangJ. LiuL.Y. LiuC.Z. Hippocampal cAMP/PKA/CREB is required for neuroprotective effect of acupuncture.Physiol. Behav.201513948249010.1016/j.physbeh.2014.12.001 25481359
     [Google Scholar]
  180. McGeerP.L. GuoJ.P. LeeM. KennedyK. McGeerE.G. PerryG. AvilaJ. TabatonM. ZhuX. Alzheimer’s disease can be spared by nonsteroidal anti-inflammatory drugs.J. Alzheimers Dis.20186231219122210.3233/JAD‑170706 29103042
     [Google Scholar]
  181. LanzaF.L. ChanF.K.L. QuigleyE.M.M. Guidelines for prevention of NSAID-related ulcer complications.Am. J. Gastroenterol.20091043728738 19240698
     [Google Scholar]
  182. KongF. JiangX. WangR. ZhaiS. ZhangY. WangD. Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease.J. Neuroinflammation202017130510.1186/s12974‑020‑01967‑2 33059746
     [Google Scholar]
  183. WangX. YinZ. CaoP. ZhengS. ChenY. YuM. LiaoC. ZhangZ. DuanY. HanJ. ZhangS. YangX. NaoXinTong Capsule ameliorates memory deficit in APP/PS1 mice by regulating inflammatory cytokines.Biomed. Pharmacother.202113311096410.1016/j.biopha.2020.110964 33197761
     [Google Scholar]
  184. JinX. LiuM.Y. ZhangD.F. ZhongX. DuK. QianP. YaoW.F. GaoH. WeiM.J. Baicalin mitigates cognitive impairment and protects neurons from microglia‐mediated neuroinflammation via suppressing NLRP 3 inflammasomes and TLR 4/NF ‐κB signaling pathway.CNS Neurosci. Ther.201925557559010.1111/cns.13086 30676698
     [Google Scholar]
  185. WangB WangY QiuJ GaoS YuS SunD LouH The STING inhibitor C-176 attenuates MPTP-induced neuroinflammation and neurodegeneration in mouse parkinsonian models.Int Immunopharmacol2023124Pt A11082710.1016/j.intimp.2023.11082737619411
     [Google Scholar]
  186. AliF. SiddiqueY.H. Bioavailability and pharmaco-therapeutic potential of luteolin in overcoming Alzheimer’s disease.CNS Neurol. Disord. Drug Targets201918535236510.2174/1871527318666190319141835 30892166
     [Google Scholar]
  187. GomesB.A.Q. SilvaJ.P.B. RomeiroC.F.R. dos SantosS.M. RodriguesC.A. GonçalvesP.R. SakaiJ.T. MendesP.F.S. VarelaE.L.P. MonteiroM.C. Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: Role of SIRT1.Oxid. Med. Cell. Longev.201820181815237310.1155/2018/8152373 30510627
     [Google Scholar]
  188. ChenD. ZhouX.Z. LeeT.H. Death-associated protein kinase 1 as a promising drug target in cancer and Alzheimer’s disease.Recent Patents Anticancer Drug Discov.201914214415710.2174/1574892814666181218170257 30569876
     [Google Scholar]
  189. OrdingA.G. Horváth-PuhóE. VeresK. GlymourM.M. RørthM. SørensenH.T. HendersonV.W. Cancer and risk of Alzheimer’s disease: Small association in a nationwide cohort study.Alzheimers Dement.202016795396410.1002/alz.12090 32432415
     [Google Scholar]
  190. SahelD.K. MittalA. ChitkaraD. CRISPR/Cas system for genome editing: Progress and prospects as a therapeutic tool.J. Pharmacol. Exp. Ther.2019370372573510.1124/jpet.119.257287 31122933
     [Google Scholar]
  191. LuL. YuX. CaiY. SunM. YangH. Application of CRISPR/Cas9 in Alzheimer’s disease.Front. Neurosci.20211580389410.3389/fnins.2021.803894 34992519
     [Google Scholar]
  192. WangT. LiuX. GuanJ. GeS. WuM.B. LinJ. YangL. Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer’s disease.Eur. J. Med. Chem.201916920022310.1016/j.ejmech.2019.02.076 30884327
     [Google Scholar]
  193. PratiF. De SimoneA. BisignanoP. ArmirottiA. SummaM. PizziraniD. ScarpelliR. PerezD.I. AndrisanoV. Perez-CastilloA. MontiB. MassenzioF. PolitoL. RacchiM. FaviaA.D. BottegoniG. MartinezA. BolognesiM.L. CavalliA. Multitarget drug discovery for Alzheimer’s disease: Triazinones as BACE-1 and GSK-3β inhibitors.Angew. Chem. Int. Ed.20155451578158210.1002/anie.201410456 25504761
     [Google Scholar]
  194. WalshN.C. KenneyL.L. JangalweS. AryeeK-E. GreinerD.L. BrehmM.A. ShultzL.D. Annual review of pathology.Mechanisms of Disease201712118721510.1146/annurev‑pathol‑052016‑100332
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266340314250303003647
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Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments
Curr. Top. Med. Chem. 25, 2585 (2025); https://doi.org/10.2174/0115680266340314250303003647
/content/journals/ctmc/10.2174/0115680266340314250303003647
/content/journals/ctmc/10.2174/0115680266340314250303003647
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  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; Cancer; drug therapy; molecular mechanisms; signaling pathways

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