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Eurasian Journal of
Medicine and Oncology NOTCH3 in CSVD and breast cancer

metastasis. Figure 2 summarises the roles of NOTCH3 induce VSMC degeneration, arterial wall remodelling
as a potential molecular link between BC and CSVD deficits, and compromised BBB integrity through increased
(i.e., CADASIL). apoptotic signalling pathways. 72,125 These pathophysiological
Recent experimental studies have further elucidated the processes contribute to the hallmark features of CSVD,
dual role of NOTCH3 signalling in both cerebrovascular including WMHs and microvascular ischemia.
and oncogenic contexts. In CSVD, particularly in CADASIL Moreover, mutations in the NOTCH3 gene lead to
models, aberrant NOTCH3 activity has been shown to the misfolding and aggregation of the receptor, resulting

Figure 2. Schematic illustration of the central role of NOTCH3 in linking BC and CSVD. In BC, NOTCH3 activation promotes tumor growth,
metastasis, and chemo-resistance, as depicted by tumor cells, the microenvironment, and blood vessels. In CSVD, NOTCH3 gene mutations
lead to VSMC degeneration, endothelial dysfunction, and ischemic stroke. A potential targeted therapy against NOTCH3 aberration may
serve as a dual strategy to potentially mitigate tumor progression in BC and prevent vascular damage in CSVD. Image created by the authors.
Abbreviations: BC: Breast cancer; CSVD: Cerebral small vessel disease; VSMC: Vascular smooth muscle cell; BBB: Blood–brain barrier; CADASIL:
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Volume 9 Issue 3 (2025) 43 doi: 10.36922/EJMO025150095