Table 2.

Significance of Notch pathway in TME-dependent drug resistance. (↑: increase; ↓: decrease).

Drugs	Targeted Notch Receptors or Ligands	Experimental Models	Evidences	References
Anastrozole, Letrozole, Exemestane	JAG1	AI resistant BC cells AI resistant BC patient samples	M2 TAM proportion ↑	[88]
Tamoxifen, Fulvestrant	IL6/Notch3 signaling activation	Hormonal therapy resistant cells In vivo xenograft BC models	CD133 high/ ER low/IL6 high CSCs self-renewal ↑	[127]
Tamoxifen	Notch 4 ↑ JAG1 ↑ Dll1-3 ↑	MCF7 Y537S-ERα cells	Mammosphere-forming efficiency ↑ Endocrine resistance	[128]
Tamoxifen, Fulvestrant,	JAG1/Notch4 activation	ALDH+/ER− BCSCs patient-derived cells In vivo patient-derived xenograft BC models	BCSCs self-renewal ↑	[129]
Lapatinib	JAG1 ↑ Notch1/3/4 ↑	HER2 overexpressing BC cells	CSCs enrichment and tumor initiation	[130]
Trastuzumab	Notch1 ↑	Trastuzumab resistant HER2+ BC cells	PTEN ↓ ERK1/2 ↑ BCSCs survival and self-renewal ↑	[131]
Paclitaxel	Notch signaling activation	ER+ and TNBC cells Xenograft BC models	HIF2α ↑ Stem phenotype	[132]