Table 3.

Application of different cell death regulators in TNBC

Cell death pathway involved	Drugs	Mechanism	Reference
Apoptosis	ABT-737	ABT-737 attaches to Bcl-2/Bcl-xL/Bcl-w, stopping them from interacting with Bax and Bak, which in turn lifts the suppression of apoptosis	[395]
	LCL161	LCL161 blocks IAPs, lifting their inhibition of apoptosis, and alters the tumor microenvironment by drawing macrophages to the tumor location	[396]
	APR-246	When p53 is activated, it increases the levels of pro-apoptotic proteins, such as Bax and PUMA, and decreases the levels of anti-apoptotic proteins such as Bcl-2 and Bcl-xL	[397, 398]
	Pembrolizumab	Blocking the PD-1/PD-L1 immune checkpoint activates CTLs and triggers cancer cell apoptosis via T cell-mediated cytotoxicity	[376, 399]
	Epothilone B	Induction of cancer cell apoptosis via the PI3K/AKT/mTOR signaling pathway enhances the apoptotic effects of ABT-737	[286]
Pyroptosis	Cisplatin	Activation of the MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC induces pyroptosis to exert anti-tumor effects	[383]
	AZU1	Regulation of the pNF-κB/NLRP3/caspase-1/GSDMD axis in TNBC promotes pyroptosis	[400]
	MCC950	By binding to the NACHT domain of NLRP3, its oligomerization and activation are prevented, which inhibits its function and makes TNBC cells more sensitive to PTX	[279]
	CY-09	Inhibiting the Walker B motif of NLRP3 reduces its activity, which in turn suppresses IL-1β/EMT/Wnt/β-catenin signaling and makes TNBC cells more sensitive to GDC-0941	[401]
	OLT1177	Inhibition of NLRP3-induced IL-1β prevents the progression of TNBC	[402]
Autophgy	CQ	Preventing the fusion of autophagosomes with lysosomes results in the buildup of autophagosomes inside the cell, which encourages the death of tumor cells	[288, 289]
	Toosendanin	Raising lysosomal pH inhibits autolysosome maturation, thereby suppressing late-stage autophagy in TNBC cells	[403]
	circEGFR	The translocation of annexin A2 (ANXA2) to the plasma membrane in TNBC cells facilitates the dissociation of the transcription factor TFEB from the ANXA2-TFEB complex, subsequently promoting autophagy. Concurrently, circEGFR acts as a competing endogenous RNA (ceRNA) by directly binding to miR-224-5p, thereby inhibiting its expression and mitigating the suppression of autophagy mediated by the miR-224-5p/ATG13/ULK1 axis	[404]
	UBC12	Enhancing TRIM25 sumoylation boosts its interaction with TFEB, which promotes the transcription and activation of genes related to autophagy	[405]
Necroptosis	ZBP1	When glucose is deprived, mtDNA is released into the cytoplasm, where it attaches to ZBP1, triggering MLKL activation in a manner dependent on Bcl-2 family proteins and NOXA	[406]
	Curcuma longa	Enhanced expression of TRAIL under acidic conditions induces necroptotic apoptosis in a RIPK1- and RIPK3-dependent manner	[407]
Ferroptosis	Erastin	Blocking System Xc- on the cell membrane lowers cystine absorption, which results in reduced GSH production inside the cell and weakened antioxidant defenses, thus encouraging lipid peroxidation and ferroptosis	[218, 219]
	Sulfasalazine	Blocking VDAC in mitochondria impairs their function, leading to the release of iron ions and heightened oxidative stress	[408, 409]
	RSL3	Inhibition of GPX4 activity elevates intracellular lipid peroxidation levels, thereby promoting ferroptosis	[292, 293]
	Liproxstatin-1	In TNBC cells, the activation of cPLA2α leads to the activation of ACSL4, which facilitates the attachment of PUFAs to coenzyme A, thereby raising lipid peroxidation levels and inducing ferroptosis	[410]
	Eupaformosanin	Ubiquitination of mutant p53 induces apoptosis and ferroptosis in TNBC cells	[320]