Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Table 1

ROS modulating drugs undergoing clinical trials in oncology.

Drug	Mechanism of action	Cancer type	Outcome	Ref.
L-Buthionine-sulfoximine	Inhibits GSH synthesis; activates PKCδ	Neuroblastoma; Melanoma	Efficacious in vitro	[67–73]
Menadione	Depletes GSH; activates ERK1/2 and p38MAPK	Gastrointestinal and lung cancer	Under clinical trial	[74–77]
Imexon	Depletes intracellular thiols; increases AP-1 and Nrf2-DNA binding activity	Advanced breast cancer; NSCLC; prostate and pancreatic tumors	Efficacious	[78–82]
Disulfiram	Oxidizes GSH and inhibits proteasome; activates JNK; inhibits Nrf2 and NF-κB	Metastatic melanoma; liver cancer	Under clinical trial	[68, 83, 84]
Bortezomib	Inhibits proteasome activity; activates NF-κB; activates Nrf2 and upregulates HO-1	Myeloma, leukemia, AML, myelodysplastic syndrome, neuroblastoma, prostate cancer	Under clinical trial	[85–90]
NOV-002	Oxidizes GSH and induces S-glutathionylation	NSCLC; breast and ovarian cancer	Efficacious	[91–93]
Ezatiostat	Inhibits GST-P1 and activates JNK/ERK	Myelodysplastic syndrome	Under clinical trial	[94]
PX-12	Inactivates Trx-1	Advanced solid tumors	Efficacious	[95–97]
Dimesna	Targets Trx and Grx	Ovarian carcinoma, NSCLC	Efficacious	[95, 98, 99]
Motexafin gadolinium	Inhibits Trx	Pancreatic, biliary and haematological cancer, renal carcinoma	Under clinical trial	[97, 100–102]
Arsenic trioxide	Oxidizes GSH and thiol enzymes	APL, melanoma	Efficacious	[68]