Table 6.

Crosstalk between ferroptosis and other regulated cell death pathways in drug-resistant cancers.

Cell Death Pathway	Crosstalk Nodes with Ferroptosis	Mechanistic Interaction	Impact on Drug Resistance	Research Examples
Apoptosis	p53, Bcl-2	p53 suppresses SLC7A11 (promotes ferroptosis) + activates Bax (promotes apoptosis); Bcl-2 upregulation → ROS scavenging (inhibits ferroptosis)	Bcl-2 overexpression → dual resistance to apoptosis/ferroptosis	Breast cancer: p53+ cells → erastin sensitivity ↑50%; Bcl-2+ cells → resistance ↑40% (286, 287)
Autophagy	NCOA4 (ferritinophagy), Beclin-1	NCOA4-mediated ferritinophagy → LIP expansion (promotes ferroptosis); Beclin-1 downregulation → autophagy inhibition (reduces ferroptosis)	Autophagy deficiency → ferroptosis resistance; ferritinophagy activation → chemo-sensitization	Pancreatic cancer: NCOA4 siRNA → ferroptosis resistance; Beclin-1 overexpression → erastin efficacy ↑35% (288, 289)
Pyroptosis	NLRP3 Inflammasome, IL-1β	NLRP3 activation → IL-1β secretion → ACSL4 upregulation (promotes ferroptosis); IL-1β → MDSC recruitment (inhibits ferroptosis)	NLRP3 deficiency → ferroptosis resistance; IL-1β blockade → chemo-sensitization	Colorectal cancer: NLRP3+ tumors → RSL3 sensitivity ↑45%; IL-1β inhibitor + erastin → tumor growth ↓60% (290, 291)