Ferroptosis regulates key signaling pathways in gastrointestinal tumors: Underlying mechanisms and therapeutic strategies

Table 2 Conventional drugs and their mode of action in ferroptosis

GI cancer	Drugs	Pathway involved	Mode of action	Ref.
Colorectal cancer	Paclitaxel	p53, SLC7A11	Lipid peroxidation by suppressing GPX4 expression	[156]
	5-fluorouracil	Lipocalin2 (LCN2), xCT	Stimulates GPX4 expression by diminishing circulating iron levels	[157]
	Cisplatin	Ferrostatin-1	Conjugates with GPX and GSH modulation	[158]
	Cetuximab	GSH, GPX4, HO-1, SLC7A11, KRAS, RSL3	Through β-elemene synergism by inducing iron dependent ROS, GSH accumulation, and EMT regulation	[159]
	Dihydro-artemisinin (DAT)	Iron metabolism, GPX4	Sensitizes cells to ferroptosis by iron overload and lysosomal degradation	[160]
Hepatocellular carcinoma	Artesunate	Ferritin	Elevates lysosomal degradation partially through autophagy along with sorafenib; it induces cathepsin activation	[161]
	Sorafenib	Nrf2	Through metallothionein-1 activation (MT-1G–Nrf2) axis	[162,125]
	Deferoxamine	Iron metabolism	Through peroxidation and iron storage depletion	[163]
Gastric cancer	Cisplatin	Nrf2/Keap1-xCT	Through transcription factor ATF3 overexpression	[164]

ATF3: Activating transcription factor 3; EMT: Epithelial-mesenchymal transition; GI: Gastrointestinal; GPX4: Glutathione peroxidase 4; GSH: Glutathione; HO-1: Heme oxygenase-1; Keap1: Kelch-like ECH-associated protein 1; Nrf2: Nuclear factor erythroid 2–related factor 2; ROS: Reactive oxygen species; RSL3: Ras-selective lethal 3; SLC7A11: Solute carrier family 7 member 11.