T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with poor response to conventional therapy, derived from hematopoietic progenitors committed to T-cell lineage. Relapsed/Refractory patients account for nearly 20% of childhood and 45% of adult cases. Aberrant Notch signaling plays a critical role in T-ALL pathogenesis and therapy resistance. Notch inhibition is a promising therapeutic target for personalized medicine, and a variety of strategies to prevent Notch activation, including γ-secretase (GS) inhibitors (GSIs) and antibodies neutralizing Notch receptors or ligands, have been developed. Disruption of apoptosis is pivotal in cancer development and progression. Different reports evidenced the interplay between Notch and the anti-apoptotic Bcl-2 family proteins in T-ALL. Although based on early research data, this review discusses recent advances in directly targeting Notch receptors and the use of validated BH3 mimetics for the treatment of T-ALL and their combined action in light of current evidence of their use.

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), extended to deeper layers or formed metastases. The poor outcomes associated with MIBC indicate the urgent need for candidate biomarkers to improve treatment strategies. Molecular characterisation of both NMIBC and MIBC, and especially the classification 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 enzymes and the differential roles played by the NOTCH 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 receptors effectively restrained BCa growth and metastasis, suggesting the potential value 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.