Editing Notch signaling pathway (section)

=== Urothelial bladder cancer ===
Loss of Notch activity is a driving event in urothelial cancer. A study identified inactivating mutations in components of the Notch pathway in over 40% of examined human bladder carcinomas. In mouse models, genetic inactivation of Notch signaling results in Erk1/2 phosphorylation leading to tumorigenesis in the urinary tract.<ref>{{cite journal | vauthors = Rampias T, Vgenopoulou P, Avgeris M, Polyzos A, Stravodimos K, Valavanis C, Scorilas A, Klinakis A | display-authors = 6 | title = A new tumor suppressor role for the Notch pathway in bladder cancer | journal = Nature Medicine | volume = 20 | issue = 10 | pages = 1199–1205 | date = October 2014 | pmid = 25194568 | doi = 10.1038/nm.3678 | s2cid = 5390234 }}</ref> As not all NOTCH receptors are equally involved in the urothelial bladder cancer, 90% of samples in one study had some level of NOTCH3 expression, suggesting that NOTCH3 plays an important role in urothelial bladder cancer. A higher level of NOTCH3 expression was observed in high-grade tumors, and a higher level of positivity was associated with a higher mortality risk. NOTCH3 was identified as an independent predictor of poor outcome. Therefore, it is suggested that NOTCH3 could be used as a marker for urothelial bladder cancer-specific mortality risk. It was also shown that NOTCH3 expression could be a prognostic immunohistochemical marker for clinical follow-up of urothelial bladder cancer patients, contributing to a more individualized approach by selecting patients to undergo control cystoscopy after a shorter time interval.<ref>{{cite journal | vauthors = Ristic Petrovic A, Stokanović D, Stojnev S, Potić Floranović M, Krstić M, Djordjević I, Skakić A, Janković Veličković L | display-authors = 6 | title = The association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients | journal = Bosnian Journal of Basic Medical Sciences | volume = 22 | issue = 4 | pages = 523–530 | date = July 2022 | pmid = 35073251 | pmc = 9392971 | doi = 10.17305/bjbms.2021.6767 }}</ref>