Signalling pathways in a nutshell: from pathogenesis to therapeutical implications in prostate cancer
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
40372974
PubMed Central
PMC12082737
DOI
10.1080/07853890.2025.2474175
Knihovny.cz E-zdroje
- Klíčová slova
- EMT, Hedgehog, NF-κB, Notch, Prostate cancer, TGF, WNT/β-catenin, castration resistance, signalling pathways, therapeutic target, β,
- MeSH
- epitelo-mezenchymální tranzice fyziologie MeSH
- lidé MeSH
- nádory prostaty * patologie metabolismus terapie farmakoterapie MeSH
- NF-kappa B metabolismus MeSH
- proteiny hedgehog metabolismus MeSH
- signální transdukce * fyziologie MeSH
- transformující růstový faktor beta metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- NF-kappa B MeSH
- proteiny hedgehog MeSH
- transformující růstový faktor beta MeSH
From tumorigenesis to the establishment of local or metastatic high-grade tumours, an integral part of the cellular lifespan relies on various signalling pathways. Particular pathways that allow cells to proliferate by creating a network of new blood vessels have been documented, whereas other pathways are primarily involved with a migration to distant body parts, partially through the process of epithelial-mesenchymal transition (EMT). This review will discuss the different signalling pathways, such as TGF-β, Cripto-1, Wnt pathways, Hedgehog, Notch and NF-κB pathways, and how they promote tumour initiation and progression by influencing diverse cellular processes and EMT in general and in benign and malignant prostate tumours. This review will discuss only the critical pathways. Therefore, many other types of signalling pathways which are related to prostate cancer will not be discussed. Possibilities for further investigation will be mentioned, as many underlying mechanisms involved in these pathways have potential as targets in future tumour therapy. This review will also introduce some novel clinical trials relating to the inhibition of signalling pathways and their clinical outcomes.
American Hospital in Tbilisi Tbilisi Georgia
Department of Clinical and Molecular Pathology Palacky University Olomouc Czech Republic
Department of Clinical and Molecular Pathology University Hospital Olomouc Czech Republic
Department of Oncology University Hospital Olomouc Czech Republic
Faculty of Medicine Georgian American University Tbilisi Georgia
Zobrazit více v PubMed
Rawla P, Rawla P.. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63–89. https://www.wjon.org/index.php/wjon/article/view/1191 doi: 10.14740/wjon1191. PubMed DOI PMC
Prostate Cancer . Prostate cancer information and overview. American Cancer Society; 2024. [cited 2024 Aug 30]. https://www.cancer.org/cancer/types/prostate-cancer.html.
EAU Guidelines. Edn. Presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6.
Lin CY, Chuu CP.. New classification may assist the development of targeted therapies for treatment-refractory castration-resistant prostate cancer. Transl Androl Urol. 2020;9(2):837–839. https://tau.amegroups.org/article/view/38875/html doi: 10.21037/tau.2020.03.24. PubMed DOI PMC
Schaeffer EM, Srinivas S, Adra N, et al. . Prostate cancer, version 4.2023, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2023;21(10):1067–1096. https://pubmed.ncbi.nlm.nih.gov/37856213/ doi: 10.6004/jnccn.2023.0050. PubMed DOI
Lundberg A, Zhang M, Aggarwal R, et al. . The genomic and epigenomic landscape of double-negative metastatic prostate cancer. Cancer Res. 2023;83(16):2763–2774. https://pmc.ncbi.nlm.nih.gov/articles/PMC10425725/ doi: 10.1158/0008-5472.CAN-23-0593. PubMed DOI PMC
Montanari M, Rossetti S, Cavaliere C, et al. . Epithelial-mesenchymal transition in prostate cancer: an overview. Oncotarget. 2017;8(21):35376–35389. https://www.oncotarget.com/article/15686/text/ doi: 10.18632/oncotarget.15686. PubMed DOI PMC
Goncharov AP, Vashakidze N, Kharaishvili G.. Epithelial-mesenchymal transition: a fundamental cellular and microenvironmental process in benign and malignant prostate pathologies. Biomedicines. 2024;12(2):418. https://www.mdpi.com/2227-9059/12/2/418 doi: 10.3390/biomedicines12020418. PubMed DOI PMC
Baghban R, Roshangar L, Jahanban-Esfahlan R, et al. . Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020;18(1):59. doi: 10.1186/s12964-020-0530-4. PubMed DOI PMC
Leivonen SK, Kähäri VM.. Transforming growth factor-beta signaling in cancer invasion and metastasis. Int J Cancer. 2007;121(10):2119–2124. https://pubmed.ncbi.nlm.nih.gov/17849476/ doi: 10.1002/ijc.23113. PubMed DOI
Massagué J, Blain SW, Lo RS.. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 2000;103(2):295–309. https://pubmed.ncbi.nlm.nih.gov/11057902/ doi: 10.1016/s0092-8674(00)00121-5. PubMed DOI
Chang H, Brown CW, Matzuk MM.. Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev. 2002;23(6):787–823. https://pubmed.ncbi.nlm.nih.gov/12466190/ doi: 10.1210/er.2002-0003. PubMed DOI
Taylor MA, Parvani JG, Schiemann WP.. The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia. 2010;15(2):169–190. https://pubmed.ncbi.nlm.nih.gov/20467795/ doi: 10.1007/s10911-010-9181-1. PubMed DOI PMC
Zavadil J, Bitzer M, Liang D, et al. . Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci U S A. 2001;98(12):6686–6691. https://pubmed.ncbi.nlm.nih.gov/11390996/ doi: 10.1073/pnas.111614398. PubMed DOI PMC
Neil JR, Johnson KM, Nemenoff RA, et al. . Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through a PGE2-dependent mechanisms. Carcinogenesis. 2008;29(11):2227–2235. https://pubmed.ncbi.nlm.nih.gov/18725385/ doi: 10.1093/carcin/bgn202. PubMed DOI PMC
Markowitz SD, Roberts AB.. Tumor suppressor activity of the TGF-beta pathway in human cancers. Cytokine Growth Factor Rev. 1996;7(1):93–102. https://pubmed.ncbi.nlm.nih.gov/8864357/ doi: 10.1016/1359-6101(96)00001-9. PubMed DOI
Furler RL, Nixon DF, Brantner CA, et al. . TGF-β sustains tumor progression through biochemical and mechanical signal transduction. Cancers. 2018;10(6):199. https://www.mdpi.com/2072-6694/10/6/199/htm doi: 10.3390/cancers10060199. PubMed DOI PMC
Hanahan D, Weinberg RA.. The hallmarks of cancer. Cell. 2000; 100(1):57–70. https://pubmed.ncbi.nlm.nih.gov/10647931/ doi: 10.1016/S0092-8674(00)81683-9. PubMed DOI
Dumont N, Arteaga CL.. Transforming growth factor-beta and breast cancer: tumor promoting effects of transforming growth factor-beta. Breast Cancer Res. 2000;2(2):125–132. https://pubmed.ncbi.nlm.nih.gov/11250702/ doi: 10.1186/bcr44. PubMed DOI PMC
Pardali K, Moustakas A.. Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta. 2007;1775(1):21–62. https://pubmed.ncbi.nlm.nih.gov/16904831/ doi: 10.1016/j.bbcan.2006.06.004. PubMed DOI
Hao Y, Baker D, Dijke PT.. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int J Mol Sci. 2019;20(11):2767. doi: 10.3390/ijms20112767. PubMed DOI PMC
Krstic J, Santibanez JF.. Transforming growth factor-beta and matrix metalloproteinases: functional interactions in tumor stroma-infiltrating myeloid cells. Sci World J. 2014;2014:1–14. doi: 10.1155/2014/521754. PubMed DOI PMC
Baba AB, Rah B, Bhat GR, et al. . Transforming growth factor-beta (TGF-β) signaling in cancer-a betrayal within. Front Pharmacol. 2022;13:791272. doi: 10.3389/fphar.2022.791272. PubMed DOI PMC
Zavadil J, Böttinger EP.. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005;24(37):5764–5774. https://pubmed.ncbi.nlm.nih.gov/16123809/ doi: 10.1038/sj.onc.1208927. PubMed DOI
Gobbi H, Arteaga CL, Jensen RA, et al. . Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas. Histopathology. 2000;36(2):168–177. https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2559.2000.00841.x doi: 10.1046/j.1365-2559.2000.00841.x. PubMed DOI
Ahmed S, Bradshaw AD, Gera S, et al. . The TGF-β/Smad4 signaling pathway in pancreatic carcinogenesis and its clinical significance. J Clin Med. 2017;6(1):5. doi: 10.3390/jcm6010005. PubMed DOI PMC
Thompson-Elliott B, Johnson R, Khan SA.. Alterations in TGFβ signaling during prostate cancer progression. Am J Clin Exp Urol. 2021;9(4):318–328. PubMed PMC
Wang Z, Zhang Y, Zhao C, et al. . The miR-223-3p/MAP1B axis aggravates TGF-β-induced proliferation and migration of BPH-1 cells. Cell Signal. 2021;84:110004. doi: 10.1016/j.cellsig.2021.110004. PubMed DOI
Jones E, Pu H, Kyprianou N.. Targeting TGF-β in prostate cancer: therapeutic possibilities during tumor progression. Expert Opin Ther Targets. 2009;13(2):227–234. https://www.tandfonline.com/doi/abs/10.1517/14728220802705696 doi: 10.1517/14728220802705696. PubMed DOI
Study Details . Study of TGF-β receptor inhibitor galunisertib (LY2157299) and enzalutamide in metastatic castration-resistant prostate cancer. ClinicalTrials.gov; 2024. https://clinicaltrials.gov/study/NCT02452008.
Rodríguez Y, Unno K, Truica MI, et al. . A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer. Cancer Res. 2022;82(11):2110–2123. https://pubmed.ncbi.nlm.nih.gov/35405009/ doi: 10.1158/0008-5472.CAN-21-3565. PubMed DOI PMC
Ottley E, Gold E.. microRNA and non-canonical TGF-β signalling: implications for prostate cancer therapy. Crit Rev Oncol Hematol. 2014;92(1):49–60. doi: 10.1016/j.critrevonc.2014.05.011. PubMed DOI
Shou M, Zhou H, Ma L.. New advances in cancer therapy targeting TGF-β signaling pathways. Mol Ther Oncolytics. 2023;31:100755. http://www.cell.com/article/S2372770523001043/fulltext doi: 10.1016/j.omto.2023.100755. PubMed DOI PMC
Castro NP, Rangel MC, Nagaoka T, et al. . Cripto-1: at the crossroads of embryonic stem cells and cancer. Embryonic stem cells – Basic biology to bioengineering; 2011. [cited 2024 Aug 30]. https://www.intechopen.com/chapters/19271.
Rodrigues Sousa E, Zoni E, Karkampouna S, et al. . A multidisciplinary review of the roles of cripto in the scientific literature through a bibliometric analysis of its biological roles. Cancers. 2020;12(6):1480. https://www.mdpi.com/2072-6694/12/6/1480/htm doi: 10.3390/cancers12061480. PubMed DOI PMC
Nickel J, Ten Dijke P, Mueller TD.. TGF-β family co-receptor function and signaling. Acta Biochim Biophys Sin. 2018;50(1):12–36. doi: 10.1093/abbs/gmx126. PubMed DOI
Ishii H, Afify SM, Hassan G, et al. . Cripto-1 as a potential target of cancer stem cells for immunotherapy. Cancers. 2021;13(10):2491. https://www.mdpi.com/2072-6694/13/10/2491/htm doi: 10.3390/cancers13102491. PubMed DOI PMC
Bianco C, Rangel MC, Castro NP, et al. . Role of cripto-1 in stem cell maintenance and malignant progression. Am J Pathol. 2010;177(2):532–540. doi: 10.2353/ajpath.2010.100102. PubMed DOI PMC
Liu Y, Qin Z, Yang K, et al. . Cripto-1 promotes epithelial-mesenchymal transition in prostate cancer via Wnt/β-catenin signaling. Oncol Rep. 2017;37(3):1521–1528. https://pubmed.ncbi.nlm.nih.gov/28098905/ doi: 10.3892/or.2017.5378. PubMed DOI
Arnouk H, Yum G, Shah D.. Cripto-1 as a key factor in tumor progression, epithelial to mesenchymal transition and cancer stem cells. Int J Mol Sci. 2021;22(17):9280. https://www.mdpi.com/1422-0067/22/17/9280/htm doi: 10.3390/ijms22179280. PubMed DOI PMC
Liu YAN, Wang J, Yang T, et al. . Overexpression levels of cripto-1 predict poor prognosis in patients with prostate cancer following radical prostatectomy. Oncol Lett. 2019;18(3):2584–2591. https://pubmed.ncbi.nlm.nih.gov/31452743/ doi: 10.3892/ol.2019.10555. PubMed DOI PMC
Tesar EC, Mikolasevic I, Skocilic I, et al. . Prostate cancer scoring index for risk of progression of radioresistant disease. JPM. 2023;13(5):870. https://www.mdpi.com/2075-4426/13/5/870/htm doi: 10.3390/jpm13050870. PubMed DOI PMC
Lawrence MG, Margaryan NV, Loessner D, et al. . Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells. Prostate. 2011;71(11):1198–1209. doi: 10.1002/pros.21335. PubMed DOI PMC
Haseeb M, Pirzada RH, Ul Ain Q, et al. . Wnt signaling in the regulation of immune cell and cancer therapeutics. Cells. 2019;8(11):1380. https://www.mdpi.com/2073-4409/8/11/1380/htm doi: 10.3390/cells8111380. PubMed DOI PMC
Jones SE, Jomary C.. Secreted Frizzled-related proteins: searching for relationships and patterns. Bioessays. 2002;24(9):811–820. https://pubmed.ncbi.nlm.nih.gov/12210517/ doi: 10.1002/bies.10136. PubMed DOI
Lechler T, Mapelli M.. Spindle positioning and its impact on vertebrate tissue architecture and cell fate. Nat Rev Mol Cell Biol. 2021;22(10):691–708. https://pubmed.ncbi.nlm.nih.gov/34158639/ doi: 10.1038/s41580-021-00384-4. PubMed DOI PMC
Moon RT, Brown JD, Yang-Snyder JA, et al. . Structurally related receptors and antagonists compete for secreted Wnt ligands. Cell. 1997;88(6):725–728. https://pubmed.ncbi.nlm.nih.gov/9118212/ doi: 10.1016/s0092-8674(00)81915-7. PubMed DOI
Yardy GW, Brewster SF.. Wnt signalling and prostate cancer. Prostate Cancer Prostatic Dis. 2005; 8(2):119–126. https://pubmed.ncbi.nlm.nih.gov/15809669/ doi: 10.1038/sj.pcan.4500794. PubMed DOI
Bilić J, Huang Y-L, Davidson G, et al. . Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science. 2007; 316(5831):1619–1622. https://pubmed.ncbi.nlm.nih.gov/17569865/ doi: 10.1126/science.1137065. PubMed DOI
Schwarz-Romond T, Fiedler M, Shibata N, et al. . The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization. Nat Struct Mol Biol. 2007;14(6):484–492. https://pubmed.ncbi.nlm.nih.gov/17529994/ doi: 10.1038/nsmb1247. PubMed DOI
He TC, Sparks AB, Rago C, et al. . Identification of c-MYC as a target of the APC pathway. Science. 1998;281(5382):1509–1512. https://pubmed.ncbi.nlm.nih.gov/9727977/ doi: 10.1126/science.281.5382.1509. PubMed DOI
Shtutman M, Zhurinsky J, Simcha I, et al. . The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A. 1999;96(10):5522–5527. https://pubmed.ncbi.nlm.nih.gov/10318916/ doi: 10.1073/pnas.96.10.5522. PubMed DOI PMC
Carlson ME, Conboy MJ, Hsu M, et al. . Relative roles of TGF-beta1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell. 2009;8(6):676–689. https://pubmed.ncbi.nlm.nih.gov/19732043/ doi: 10.1111/j.1474-9726.2009.00517.x. PubMed DOI PMC
Rahmani M, Read JT, Carthy JM, et al. . Regulation of the versican promoter by the beta-catenin-T-cell factor complex in vascular smooth muscle cells. J Biol Chem. 2005;280(13):13019–13028. https://pubmed.ncbi.nlm.nih.gov/15668231/ doi: 10.1074/jbc.M411766200. PubMed DOI
Haertel-Wiesmann M, Liang Y, Fantl WJ, et al. . Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial cells. J Biol Chem. 2000; 275(41):32046–32051. https://pubmed.ncbi.nlm.nih.gov/10884377/ doi: 10.1074/jbc.M000074200. PubMed DOI
ten Berge D, Koole W, Fuerer C, et al. . Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell. 2008;3(5):508–518. https://pubmed.ncbi.nlm.nih.gov/18983966/ doi: 10.1016/j.stem.2008.09.013. PubMed DOI PMC
Anthony CC, Robbins DJ, Ahmed Y, et al. . Nuclear regulation of Wnt/β-catenin signaling: it’s a complex situation. Genes 2020;11(8):886. doi: 10.3390/genes11080886. PubMed DOI PMC
Gavert N, Ben-Ze’ev A.. Beta-catenin signaling in biological control and cancer. J of Cellular Biochemistry. 2007;102(4):820–828. https://pubmed.ncbi.nlm.nih.gov/17854061/ doi: 10.1002/jcb.21505. PubMed DOI
Kushima R, Tsukashita S, Hattori T.. Role of immunohistochemical expression of beta-catenin and mucin in stomach cancer. In: Handbook of immunohistochemistry and in situ hybridization of human carcinomas. vol. 4. London: Elsevier; 2006. p. 157–160.
Uchino M, Kojima H, Wada K, et al. . Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells. BMC Cancer. 2010; 10(1):414. doi: 10.1186/1471-2407-10-414. PubMed DOI PMC
Ng TL, Gown AM, Barry TS, et al. . Nuclear beta-catenin in mesenchymal tumors. Mod Pathol. 2005;18(1):68–74. https://pubmed.ncbi.nlm.nih.gov/15375433/ doi: 10.1038/modpathol.3800272. PubMed DOI
Ishitani T, Ninomiya-Tsuji J, Nagai S, et al. . The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature. 1999;399(6738):798–802. https://pubmed.ncbi.nlm.nih.gov/10391247/ doi: 10.1038/21674. PubMed DOI
Voronkov A, Krauss S.. Wnt/beta-catenin signaling and small molecule inhibitors. CPD. 2012;19(4):634–664. doi: 10.2174/13816128130406. PubMed DOI PMC
Ma B, Hottiger MO.. Crosstalk between Wnt/β-Catenin and NF-κB signaling pathway during inflammation. Front Immunol. 2016;7:378. https://pubmed.ncbi.nlm.nih.gov/27713747/ doi: 10.3389/fimmu.2016.00378. PubMed DOI PMC
Patni AP, Harishankar MK, Joseph JP, et al. . Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications. Cell Oncol. 2021;44(3):473–494. https://pubmed.ncbi.nlm.nih.gov/33704672/ doi: 10.1007/s13402-021-00591-3. PubMed DOI
Kumar V, Vashishta M, Kong L, et al. . The role of Notch, Hedgehog, and Wnt Signaling pathways in the resistance of tumors to anticancer therapies. Front Cell Dev Biol. 2021;9:650772. doi: 10.3389/fcell.2021.650772. PubMed DOI PMC
Zhang Z, Cheng L, Li J, et al. . Inhibition of the Wnt/β-catenin pathway overcomes resistance to enzalutamide in castration-resistant prostate cancer. Cancer Res. 2018;78(12):3147–3162. https://pubmed.ncbi.nlm.nih.gov/29700003/ doi: 10.1158/0008-5472.CAN-17-3006. PubMed DOI PMC
Patel R, Brzezinska EA, Repiscak P, et al. . Activation of β-catenin cooperates with loss of Pten to drive AR-independent castration-resistant prostate cancer. Cancer Res. 2020;80(3):576–590. https://pubmed.ncbi.nlm.nih.gov/31719098/ doi: 10.1158/0008-5472.CAN-19-1684. PubMed DOI
Shorning BY, Dass MS, Smalley MJ, et al. . The PI3K-AKT-mtor pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT Signaling. Int J Mol Sci. 2020;21(12):1–47. https://pubmed.ncbi.nlm.nih.gov/32630372/ PubMed PMC
Katoh M. Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β-catenin signaling activation. Int J Mol Med. 2018;42(2):713–725. https://pubmed.ncbi.nlm.nih.gov/29786110/ doi: 10.3892/ijmm.2018.3689. PubMed DOI PMC
Kaplan Z, Zielske SP, Ibrahim KG, et al. . Wnt and β-catenin signaling in the bone metastasis of prostate cancer. Life. 2021;11(10):1099. https://www.mdpi.com/2075-1729/11/10/1099/htm doi: 10.3390/life11101099. PubMed DOI PMC
Study Details . Predictive value of progastrin titer at diagnosis and of progastrin kinetics during treatment in cancer patients. ClinicalTrials.gov; 2024. https://www.clinicaltrials.gov/study/NCT03787056.
Yashi M, Nishihara D, Yokoyama M, et al. . Plasma progastrin-releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis-targeted agents in patients with metastatic castration-resistant prostate cancer. Cancer Rep. 2023;6(3):e1762. https://pubmed.ncbi.nlm.nih.gov/36470854/ doi: 10.1002/cnr2.1762. PubMed DOI PMC
Chen G, Shukeir N, Potti A, et al. . Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer. 2004;101(6):1345–1356. https://pubmed.ncbi.nlm.nih.gov/15316903/ doi: 10.1002/cncr.20518. PubMed DOI
Robinson D, Van Allen EM, Wu Y-M, et al. . Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215–1228. http://www.cell.com/article/S0092867415005486/fulltext doi: 10.1016/j.cell.2015.05.001. PubMed DOI PMC
Beltran H, Yelensky R, Frampton GM, et al. . Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013;63(5):920–926. https://pubmed.ncbi.nlm.nih.gov/22981675/ doi: 10.1016/j.eururo.2012.08.053. PubMed DOI PMC
Grasso CS, Wu Y-M, Robinson DR, et al. . The mutational landscape of lethal castrate resistant prostate cancer. Nature. 2012;487(7406):239–243. doi: 10.1038/nature11125. PubMed DOI PMC
Voeller HJ, Truica CI, Gelmann EP.. Beta-catenin mutations in human prostate cancer. Cancer Res. 1998;58(12):2520–2523. PubMed
Pan K-F, Lee W-J, Chou C-C, et al. . Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer. Embo J. 2021;40(4):e105450. https://www.embopress.org/doi/10.15252/embj.2020105450 doi: 10.15252/embj.2020105450. PubMed DOI PMC
Kühl M. Non-canonical Wnt signaling in Xenopus: regulation of axis formation and gastrulation. Semin Cell Dev Biol. 2002;13(3):243–249. doi: 10.1016/s1084-9521(02)00050-2. PubMed DOI
McEwen DG, Cox RT, Peifer M.. The canonical Wg and JNK signaling cascades collaborate to promote both dorsal closure and ventral patterning. Development. 2000;127(16):3607–3617. https://pubmed.ncbi.nlm.nih.gov/10903184/ doi: 10.1242/dev.127.16.3607. PubMed DOI
Veeman MT, Axelrod JD, Moon RT.. A second canon: functions and mechanisms of β-catenin-independent Wnt signaling. Dev Cell. 2003;5(3):367–377. doi: 10.1016/s1534-5807(03)00266-1. PubMed DOI
Turashvili G, Bouchal J, Burkadze G, et al. . Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology. 2006;73(5):213–223. doi: 10.1159/000098207. PubMed DOI
Slusarski DC, Corces VG, Moon RT.. Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature. 1997;390(6658):410–413. https://pubmed.ncbi.nlm.nih.gov/9389482/ doi: 10.1038/37138. PubMed DOI
Ahumada A, Slusarski DC, Liu X, et al. . Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science. 2002;298(5600):2006–2010. https://pubmed.ncbi.nlm.nih.gov/12471263/ doi: 10.1126/science.1073776. PubMed DOI
Sheldahl LC, Park M, Malbon CC, et al. . Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 1999;9(13):695–698. doi: 10.1016/s0960-9822(99)80310-8. PubMed DOI
Pandur P, Läsche M, Eisenberg LM, et al. . Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature. 2002;418(6898):636–641. https://pubmed.ncbi.nlm.nih.gov/12167861/ doi: 10.1038/nature00921. PubMed DOI
Heisenberg CP, Tada M, Rauch GJ, et al. . Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature. 2000;405(6782):76–81. https://pubmed.ncbi.nlm.nih.gov/10811221/ doi: 10.1038/35011068. PubMed DOI
Veeman MT, Slusarski DC, Kaykas A, et al. . Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements. Curr Biol. 2003;13(8):680–685. https://pubmed.ncbi.nlm.nih.gov/12699626/ doi: 10.1016/s0960-9822(03)00240-9. PubMed DOI
van Amerongen R, Nusse R.. Towards an integrated view of Wnt signaling in development. Development. 2009;136(19):3205–3214. https://pubmed.ncbi.nlm.nih.gov/19736321/ doi: 10.1242/dev.033910. PubMed DOI
Yamamoto S, Nishimura O, Misaki K, et al. . Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15(1):23–36. https://pubmed.ncbi.nlm.nih.gov/18606138/ doi: 10.1016/j.devcel.2008.05.007. PubMed DOI
Kharaishvili G, Simkova D, Makharoblidze E, et al. . Wnt signaling in prostate development and carcinogenesis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155(1):11–18. https://pubmed.ncbi.nlm.nih.gov/21475372/ doi: 10.5507/bp.2011.016. PubMed DOI
Topol L, Jiang X, Choi H, et al. . Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol. 2003;162(5):899–908. https://pubmed.ncbi.nlm.nih.gov/12952940/ doi: 10.1083/jcb.200303158. PubMed DOI PMC
He Y, Xu W, Xiao YT, et al. . Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduct Target Ther. 2022;7(1):198. https://www.nature.com/articles/s41392-022-01042-7 doi: 10.1038/s41392-022-01042-7. PubMed DOI PMC
Wang Y, Singhal U, Qiao Y, et al. . Wnt signaling drives prostate cancer bone metastatic tropism and invasion. Transl Oncol. 2020;13(4):100747. doi: 10.1016/j.tranon.2020.100747. PubMed DOI PMC
Li Q, Ye L, Zhang X, et al. . FZD8, a target of p53, promotes bone metastasis in prostate cancer by activating canonical Wnt/β-catenin signaling. Cancer Lett. 2017;402:166–176. doi: 10.1016/j.canlet.2017.05.029. PubMed DOI
Ma F, Arai S, Wang K, et al. . Autocrine canonical Wnt signaling primes noncanonical signaling through ROR1 in metastatic castration-resistant prostate cancer. Cancer Res. 2022;82(8):1518–1533. https://pubmed.ncbi.nlm.nih.gov/35131873/ doi: 10.1158/0008-5472.CAN-21-1807. PubMed DOI PMC
Mariadason JM, Bordonaro M, Aslam F, et al. . Down-regulation of beta-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Res. 2001;61(8):3465–3471. https://pubmed.ncbi.nlm.nih.gov/11309309/ PubMed
Naishiro Y, Yamada T, Takaoka AS, et al. . Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation. Cancer Res. 2001;61(6):2751–2758. PubMed
Li J, Zhou BP.. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11(1):49. https://pubmed.ncbi.nlm.nih.gov/21284870/ doi: 10.1186/1471-2407-11-49. PubMed DOI PMC
Schambony A, Kunz M, Gradl D.. Cross-regulation of Wnt signaling and cell adhesion. Differentiation. 2004;72(7):307–318. doi: 10.1111/j.1432-0436.2004.07207002.x. PubMed DOI
Sasaki H, Yu C-Y, Dai M, et al. . Elevated serum periostin levels in patients with bone metastases from breast but not lung cancer. Breast Cancer Res Treat. 2003;77(3):245–252. https://pubmed.ncbi.nlm.nih.gov/12602924/ doi: 10.1023/a:1021899904332. PubMed DOI
Zheng P-S, Wen J, Ang LC, et al. . Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB J. 2004;18(6):754–756. https://pubmed.ncbi.nlm.nih.gov/14766798/ doi: 10.1096/fj.03-0545fje. PubMed DOI
Nikitovic D, Zafiropoulos A, Katonis P, et al. . Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. IUBMB Life. 2006;58(1):47–53. https://pubmed.ncbi.nlm.nih.gov/16540432/ doi: 10.1080/15216540500531713. PubMed DOI
Kim L, Kimmel AR.. GSK3, a master switch regulating cell-fate specification and tumorigenesis. Curr Opin Genet Dev. 2000;10(5):508–514. doi: 10.1016/s0959-437x(00)00120-9. PubMed DOI
Gao S, Wang S, Zhao Z, et al. . TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling. Nat Commun. 2022;13(1):2792. https://www.nature.com/articles/s41467-022-30409-1 doi: 10.1038/s41467-022-30409-1. PubMed DOI PMC
Iriana S, Asha K, Repak M, et al. . Hedgehog signaling: implications in cancers and viral infections. Int J Mol Sci. 2021;22(3):1042. https://www.mdpi.com/1422-0067/22/3/1042/htm doi: 10.3390/ijms22031042. PubMed DOI PMC
Jing J, Wu Z, Wang J, et al. . Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies. Signal Transduct Target Ther. 2023;8(1):315. https://www.nature.com/articles/s41392-023-01559-5 doi: 10.1038/s41392-023-01559-5. PubMed DOI PMC
Petrova R, Joyner AL.. Roles for Hedgehog signaling in adult organ homeostasis and repair. Development. 2014;141(18):3445–3457. doi: 10.1242/dev.083691. PubMed DOI PMC
Ingham PW. Hedgehog signaling. Curr Top Dev Biol. 2022;149:1–58. https://pubmed.ncbi.nlm.nih.gov/35606054/ doi: 10.1016/bs.ctdb.2022.04.003. PubMed DOI
Onodera S, Nakamura Y, Azuma T.. Gorlin syndrome: recent advances in genetic testing and molecular and cellular biological research. Int J Mol Sci. 2020;21(20):7559. https://www.mdpi.com/1422-0067/21/20/7559/htm doi: 10.3390/ijms21207559. PubMed DOI PMC
Miller SJ, Lavker RM, Sun TT.. Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta. 2005;1756(1):25–52. https://pubmed.ncbi.nlm.nih.gov/16139432/ doi: 10.1016/j.bbcan.2005.07.003. PubMed DOI
Gonnissen A, Isebaert S, Haustermans K.. Hedgehog signaling in prostate cancer and its therapeutic implication. Int J Mol Sci. 2013;14(7):13979–14007. https://www.mdpi.com/1422-0067/14/7/13979/htm doi: 10.3390/ijms140713979. PubMed DOI PMC
Efstathiou E, Karlou M, Wen S, et al. . Integrated Hedgehog signaling is induced following castration in human and murine prostate cancers. Prostate. 2013;73(2):153–161. https://onlinelibrary.wiley.com/doi/full/10.1002/pros.22550 doi: 10.1002/pros.22550. PubMed DOI PMC
Sheng T, Li C, Zhang X, et al. . Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer. 2004;3(1):29. https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-3-29 doi: 10.1186/1476-4598-3-29. PubMed DOI PMC
De SK. Targeted therapy: small molecules. In: Medicines for cancer; 2023. p. 205–411 [cited 2024 Aug 30]. https://linkinghub.elsevier.com/retrieve/pii/B9780443133121000027.
Study Details . A pre surgical study of LDE225 in men with high-risk localized prostate cancer. ClinicalTrials.gov. 2024. [cited 2024 Feb 18]. https://clinicaltrials.gov/study/NCT02111187.
Ross AE, Hughes RM, Glavaris S, et al. . Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy. Oncotarget. 2017;8(61):104182–104192. doi: 10.18632/oncotarget.22115. PubMed DOI PMC
Katoh M, Katoh M.. Notch signaling in gastrointestinal tract. Int J Oncol. 2007;30(1):247–251. doi: 10.3892/ijo.30.1.247/abstract PubMed DOI
Ellisen LW, Bird J, West DC, et al. . TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66(4):649–661. https://pubmed.ncbi.nlm.nih.gov/1831692/ doi: 10.1016/0092-8674(91)90111-b. PubMed DOI
Fan X, Mikolaenko I, Elhassan I, et al. . Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 2004;64(21):7787–7793. https://pubmed.ncbi.nlm.nih.gov/15520184/ doi: 10.1158/0008-5472.CAN-04-1446. PubMed DOI
Dang TP, Gazdar AF, Virmani AK, et al. . Chromosome 19 translocation, overexpression of Notch3, and human lung cancer. J Natl Cancer Inst. 2000;92(16):1355–1357. https://pubmed.ncbi.nlm.nih.gov/10944559/ doi: 10.1093/jnci/92.16.1355. PubMed DOI
Park JT, Li M, Nakayama K, et al. . Notch3 gene amplification in ovarian cancer. Cancer Res. 2006;66(12):6312–6318. https://pubmed.ncbi.nlm.nih.gov/16778208/ doi: 10.1158/0008-5472.CAN-05-3610. PubMed DOI
Reedijk M, Odorcic S, Chang L, et al. . High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–8537. https://pubmed.ncbi.nlm.nih.gov/16166334/ doi: 10.1158/0008-5472.CAN-05-1069. PubMed DOI
Pece S, Serresi M, Santolini E, et al. . Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol. 2004;167(2):215–221. https://pubmed.ncbi.nlm.nih.gov/15492044/ doi: 10.1083/jcb.200406140. PubMed DOI PMC
Radtke F, Raj K.. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer. 2003;3(10):756–767. https://pubmed.ncbi.nlm.nih.gov/14570040/ doi: 10.1038/nrc1186. PubMed DOI
Proweller A, Tu L, Lepore JJ, et al. . Impaired notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res. 2006;66(15):7438–7444. https://pubmed.ncbi.nlm.nih.gov/16885339/ doi: 10.1158/0008-5472.CAN-06-0793. PubMed DOI
Acar A, Hidalgo-Sastre A, Leverentz MK, et al. . Inhibition of Wnt signalling by Notch via two distinct mechanisms. Sci Rep. 2021;11(1):9096. https://www.nature.com/articles/s41598-021-88618-5 doi: 10.1038/s41598-021-88618-5. PubMed DOI PMC
Shang Y, Smith S, Hu X.. Role of Notch signaling in regulating innate immunity and inflammation in health and disease. Protein Cell. 2016;7(3):159–174. doi: 10.1007/s13238-016-0250-0. PubMed DOI PMC
Wang Z, Li Y, Kong D, et al. . The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets. 2010;11(6):745–751. https://pubmed.ncbi.nlm.nih.gov/20041844/ doi: 10.2174/138945010791170860. PubMed DOI PMC
Stacy AJ, Craig MP, Sakaram S, et al. . ΔNp63α and microRNAs: leveraging the epithelial-mesenchymal transition. Oncotarget. 2017;8(2):2114–2129. https://www.oncotarget.com/article/13797/text/ doi: 10.18632/oncotarget.13797. PubMed DOI PMC
Orzechowska MJ, Anusewicz D, Bednarek AK.. Age- and stage-dependent prostate cancer aggressiveness associated with differential Notch signaling. Int J Mol Sci. 2022;24(1):164. https://pubmed.ncbi.nlm.nih.gov/36613607/ doi: 10.3390/ijms24010164. PubMed DOI PMC
Zinger A, Cho WC, Ben-Yehuda A.. Cancer and aging – the inflammatory connection. Aging Dis. 2017;8(5):611–627. doi: 10.14336/AD.2016.1230. PubMed DOI PMC
Marignol L, Rivera-Figueroa K, Lynch T, et al. . Hypoxia, notch signalling, and prostate cancer. Nat Rev Urol. 2013;10(7):405–413. https://pubmed.ncbi.nlm.nih.gov/23712204/ doi: 10.1038/nrurol.2013.110. PubMed DOI PMC
Torchinsky A, Toder V.. To die or not to die: the function of the transcription factor NF-kappaB in embryos exposed to stress. Am J Reprod Immunol. 2004;51(2):138–143. https://pubmed.ncbi.nlm.nih.gov/14748840/ doi: 10.1046/j.8755-8920.2003.00134.x. PubMed DOI
Häcker H, Karin M.. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006;2006(357):re13. https://www.science.org/doi/10.1126/stke.3572006re13 PubMed DOI
Karin M, Cao Y, Greten FR, et al. . NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2002;2(4):301–310. https://pubmed.ncbi.nlm.nih.gov/12001991/ doi: 10.1038/nrc780. PubMed DOI
Chua HL, Bhat-Nakshatri P, Clare SE, et al. . NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene. 2007;26(5):711–724. https://www.nature.com/articles/1209808 doi: 10.1038/sj.onc.1209808. PubMed DOI
Shang Z, Yu J, Sun L, et al. . LncRNA PCAT1 activates AKT and NF-κB signaling in castration-resistant prostate cancer by regulating the PHLPP/FKBP51/IKKα complex. Nucleic Acids Res. 2019;47(8):4211–4225. https://pubmed.ncbi.nlm.nih.gov/30773595/ doi: 10.1093/nar/gkz108. PubMed DOI PMC
Oh A, Pardo M, Rodriguez A, et al. . NF-κB signaling in neoplastic transition from epithelial to mesenchymal phenotype. from:/pmc/articles/PMC10585759/. Cell Commun Signal. 2023;21(1):291. doi: 10.1186/s12964-023-01207-z. PubMed DOI PMC
Solanas G, Porta-de-la-Riva M, Agustí C, et al. . E-cadherin controls β-catenin and NF-κB transcriptional activity in mesenchymal gene expression. J Cell Sci. 2008;121(Pt 13):2224–2234. doi: 10.1242/jcs.021667. PubMed DOI
Tripathi V, Popescu NC, Zimonjic DB.. DLC1 suppresses NF-κB activity in prostate cancer cells due to its stabilizing effect on adherens junctions. Springerplus. 2014;3(1):27. https://springerplus.springeropen.com/articles/10.1186/2193-1801-3-27 doi: 10.1186/2193-1801-3-27. PubMed DOI PMC
Zhou X, Yang XY, Popescu NC.. Preclinical evaluation of combined antineoplastic effect of DLC1 tumor suppressor protein and suberoylanilide hydroxamic acid on prostate cancer cells. Biochem Biophys Res Commun. 2012;420(2):325–330. doi: 10.1016/j.bbrc.2012.02.158. PubMed DOI PMC
Jain S, Dash P, Minz AP, et al. . Lipopolysaccharide (LPS) enhances prostate cancer metastasis potentially through NF-κB activation and recurrent dexamethasone administration fails to suppress it in vivo. Prostate. 2019;79(2):168–182. https://pubmed.ncbi.nlm.nih.gov/30264470/ doi: 10.1002/pros.23722. PubMed DOI
Yu H, Lin L, Zhang Z, et al. . Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 2020;5(1):209. https://www.nature.com/articles/s41392-020-00312-6 doi: 10.1038/s41392-020-00312-6. PubMed DOI PMC
Jain G, Cronauer MV, Schrader M, et al. . NF-κB signaling in prostate cancer: a promising therapeutic target? World J Urol. 2012;30(3):303–310. https://link.springer.com/article/10.1007/s00345-011-0792-y doi: 10.1007/s00345-011-0792-y. PubMed DOI
Ko YS, Pyo JS, Cho WJ.. Roles of NF-κB activation in benign prostatic hyperplasia and association between NF-κB and HIF-1α. Pathol Res Pract. 2022;237:154021. https://pubmed.ncbi.nlm.nih.gov/35901596/ doi: 10.1016/j.prp.2022.154021. PubMed DOI
Capece D, Verzella D, Flati I, et al. . NF-κB: blending metabolism, immunity, and inflammation. Trends Immunol. 2022;43(9):757–775. https://pubmed.ncbi.nlm.nih.gov/35965153/ doi: 10.1016/j.it.2022.07.004. PubMed DOI
Chen B, Liu X, Yu P, et al. . H. pylori-induced NF-κB-PIEZO1-YAP1-CTGF axis drives gastric cancer progression and cancer-associated fibroblast-mediated tumour microenvironment remodelling. Clin Transl Med. 2023;13(11):e1481. https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.1481 doi: 10.1002/ctm2.1481. PubMed DOI PMC
Zhang M, Liu ZZ, Aoshima K, et al. . CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Sci Transl Med. 2022;14(630):eabf5473. https://pubmed.ncbi.nlm.nih.gov/35108062/ doi: 10.1126/scitranslmed.abf5473. PubMed DOI PMC
Lin S-C, Liao Y-C, Chen P-M, et al. . Periostin promotes ovarian cancer metastasis by enhancing M2 macrophages and cancer-associated fibroblasts via integrin-mediated NF-κB and TGF-β2 signaling. J Biomed Sci. 2022;29(1):109. https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-022-00888-x doi: 10.1186/s12929-022-00888-x. PubMed DOI PMC
Voronova V, Vislobokova A, Mutig K, et al. . Combination of immune checkpoint inhibitors with radiation therapy in cancer: a hammer breaking the wall of resistance. Front Oncol. 2022;12:1035884. doi: 10.3389/fonc.2022.1035884. PubMed DOI PMC
Miller DR, Ingersoll MA, Teply BA, et al. Combination treatment options for castration-resistant prostate cancer. Prostate Cancer; 2021. [cited 2024 Aug 30]. https://pubmed.ncbi.nlm.nih.gov/34181378/. PubMed
Siewe N, Friedman A.. Combination therapy for mCRPC with immune checkpoint inhibitors, ADT and vaccine: a mathematical model. PLOS One. 2022;17(1):e0262453. doi: 10.1371/journal.pone.0262453. PubMed DOI PMC
Nakazawa M, Paller C, Kyprianou N.. Mechanisms of therapeutic resistance in prostate cancer. Curr Oncol Rep. 2017;19(2):13. https://pubmed.ncbi.nlm.nih.gov/28229393/ doi: 10.1007/s11912-017-0568-7. [InsertedFromOnline PubMed DOI PMC
Choi HY, Chang JE, Choi HY, et al. . Targeted therapy for cancers: from ongoing clinical trials to FDA-approved drugs. Int J Mol Sci. 2023;24(17):13618. https://www.mdpi.com/1422-0067/24/17/13618/htm doi: 10.3390/ijms241713618. PubMed DOI PMC
Pak S, Park S, Kim Y, et al. . The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway. J Exp Clin Cancer Res. 2019;38(1):342. 1–13. https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1342-5 doi: 10.1186/s13046-019-1342-5. PubMed DOI PMC
Cui D, Dai J, Keller JM, et al. . Notch pathway inhibition using PF-03084014, a γ-secretase inhibitor (GSI), enhances the anti-tumor effect of docetaxel in prostate cancer. Clin Cancer Res. 2015;21(20):4619–4629. doi: 10.1158/1078-0432.CCR-15-0242. PubMed DOI PMC
Yu F, Yu C, Li F, et al. . Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther. 2021;6(1):307. doi: 10.1038/s41392-021-00701-5. PubMed DOI PMC
Nguyen DP, Li J, Yadav SS, et al. . Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer. BJU Int. 2014;114(2):168–176. https://pubmed.ncbi.nlm.nih.gov/24215139/ doi: 10.1111/bju.12488. PubMed DOI