Table 3.

Reversing anti-tumor therapy resistance together with ferroptosis inducers.

Treatment	Drugs	Drugs	Target	Cancer type	Mechanism	References
Chemotherapy	Cisplatin	Erastin	ROS	NSCLC	SAHA and erastin can strongly enhance the effect of cisplatin in WT EGFR cells	(32)
		Erastin	System Xc-	Ovarian cancer	Erastin can inhibit system Xc– and potentiate the cytotoxic effects of cisplatin to eradicate tumor cells	(31)
		Erastin/sorafenib	ROS	NSCLC	Erastin/sorafenib induces cisplatin-resistant lung cancer cell ferroptosis through inhibiting the NRF2/SLC7A11 pathway	(77)
		Erastin/RSL3/STAT3 inhibitor	GPX4	Osteosarcoma	Impairing STAT3/NRF2/GPX4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin	(78)
		Gefitinib/Erlotinib	ROS	Lung cancer	Inhibition of EGFR-ERK/AKT by gefitinib activates FOXO3a, which in turn reduces ROS	(32)
	Cisplatin/etoposide	Withaferin A	GPX4	Neuroblastoma	Inhibition of GPX4 by withaferin A efficiently kills chemo-resistant neuroblastoma cells	(79)
	Gemcitabine	CN-A and PEITC	–	Pancreatic cancer	The combined treatment with CN-A and PEITC synergistically increases the ROS levels	(52)
	TMZ	ALZ003	GPX4, Lipid peroxidation	Glioblastoma	AR suppressor ALZ003 can inhibit TMZ-resistant glioblastoma through inhibiting GPX4	(34)
		Erastin	GPX4, System Xc-, Transsulfuration pathway	Glioblastoma multiforme	TMZ-inducible system Xc- upregulation and CTH activation are involved in TMZ-resistance. Erastin can block SLC7A11 and reduce CTH activity	(29)
	Docetaxel	Erastin	SLC7A11	Ovarian Cancer	Erastin can conspicuously reverse the ABCB1-mediated DTXL resistance by limiting the drug efflux activity of ABCB1	(80)
		BLZ945	CD8+T cell	Ovarian Cancer	BLZ945 together with docetaxel can increase the infiltration of CD8+ T cells in tumor tissues	(81)
	SSZ	Dyclonine	ALDH, GSH	HNSCC	Simultaneous inhibition of ALDH and depletion of GSH leads to accumulation of the cytotoxic aldehyde 4-HNE and consequent cell death
		Oxyfedrine	ALDH, GSH	Colorectal cancer		(82)
				HNSCC
	DAT	RSL3	Ferritin	Lung cancer	DAT induces lysosomal degradation of ferritin and impinges on IRP/IRE-controlled iron homeostasis to increase cellular free iron	(19)
				Colorectal cancer
				Breast cancer
	Artesunate	Cisplatin	Fe	Head and neck cancer	Artesunate activates the NRF2-ARE pathway which contributes to ferroptosis resistance	(16)
Target therapy	Lapatinib	RSL3/ML210	GPX4	Breast cancer	Persistent cells acquire a dependency on GPX4. Loss of GPX4 function results in selective ferroptosis in persistent cell	(83)
	Vemurafenib	Erastin/RSL3	System xc-, GPX4	Melanoma	The combination treatment of erastin and RSL3 results in an increase in ferroptosis sensitivity	(7)
	Gefitinib/erlotinib	Cisplatin	ROS	Lung cancer	Inhibition of EGFR-ERK/AKT by gefitinib activates FOXO3a, which in turn reduces ROS	(32)
Radiotherapy	X-ray irradiation	Oxyfedrine	GSH	Colorectal cancer	Simultaneous inhibition of ALDH and depletion of GSH leads to accumulation of the cytotoxic aldehyde 4-HNE and consequent cell death	(82)
				HNSCC
		Erastin	GPX4	NSCLC	GPX4 expression is increased in the radioresistant cells and erastin inhibits GPX4 expression	(84)
		Erastin/SSZ/RSL3/ ML162/FIN56	System xc-, GPX4, ACSL4	NSCL	IR- or KEAP1 deficiency-induced SLC7A11 expression promotes radio-resistance through inhibiting ferroptosis	(71)
				Esophageal cancer
	RT-MPs	Anti-PD-1	–	Lung carcinoma	RT-MPs polarize M2-TAMs into M1-TAMs. TAMs increase the expression of PD-L1, which enhances the follow-up effect of combined therapy with anti-PD-1	(85)
				Melonoma
Other therapy	Lovastatin	Gefitinib	GPX4	NSCLC	Down-regulation of RAS protein leads to inhibition of both the RAF/ERK and AKT pathways	(86)
	Atorvastatin	Gefitinib	GPX4	NSCLC	Down-regulation of RAS protein leads to inhibition of both the RAF/ERK and AKT pathways	(87)
	Simvastatin	Erlotinib/Gefitinib	GPX4	NSCLC	Statin may overcome the EGFR-TKI-resistance through AKT/β-catenin signal-dependent reduction of surviving	(88)
	Prominin2	RSL3/ML210/ FIN56/Erastin	Ferritin	Breast cancer	Prominin2 promotes the formation of ferritin-containing MVBs and exosomes that transport iron out of the cell	(76)

RT-MPs, Irradiated tumor cell-released microparticles; SSZ, Sulfasalazine; TMZ, Temozolomide; CN-A, Cotylenin A; PEITC, Phenethyl isothiocyanate; HNSCC, Head and neck squamous cell carcinoma; NSCLC, Non-small cell lung cancer; EGFR, Epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; DAT, Dihydro-artemisinin; AR, Androgen receptor; WT, wild-type; TAM, Tumor-associated macrophage; MVBs, multivesicular bodies.