NOTCH3 and cancer: Furthermore, hypoxia has also been shown to contribute to cancer resistance to radiotherapy; studies show that the hypoxic tumour microenvironment might induce stromal cell production of exosomes loaded with 5′-triphosphate RNA, this works as a simultaneous activator of RIG-1 and Notch3 signalling in breast cancer cells, which facilitates differentiation of radiation-resistant cancer cells (Boelens et al., 2014; Gilreath et al., 2020).