Bladder cancer: uncovering the predictive role of NOTCH as an emerging candidate biomarker for therapeutic strategies

Bladder cancer (BCa) is one of the most diagnosed cancers worldwide. It is classified as non-muscle-invasive (NMIB), confined to the mucosa, and muscle-invasive (MIB), ex-tended to deeper layers or formed metastases. The poor outcomes associated with MIBC indicate the urgent need for candidate biomarkers to improve treatment strate-gies. Molecular characterisation of both NMIBC and MIBC, and especially the classifi-cation of tumours into molecular subtypes, could provide the development of novel therapeutics in high-risk muscle-invasive bladder cancer. A few studies have focused on pathways implicated in MIBC, including growth factors, DNA–RNA modifying en-zymes and the differential roles played by the N OTCH receptors. NOTCH1 has been revealed as a tumour suppressor; in contrast, NOTCH2 and NOTCH3 have demonstrated an oncogenic role in BCa. Recent reports have found that NOTCH2 and NOTCH3 are associated with poor prognosis. Moreover, inhibiting these NOTCH re-ceptors effectively restrained BCa growth and metastasis, suggesting the potential val-ue of targeting NOTCH as a promising therapeutic strategy for bladder cancer. Given the crucial role of the NOTCH pathway, we will discuss the different predictive value of the four NOTCH receptors and the potential of NOTCH-combined therapy in BCa.