Progress in the research of cuproptosis and possible targets for cancer therapy

Table 1 Copper-related compounds and their antitumor mechanism

Compounds	Mechanism	Ref.
Elesclomol	Transferring copper ions to mitochondria and increasing ROS level	Nagai et al[7]
Flavonoid drugs	Interfering with copper ion redox and inducing mitochondrial apoptosis	Liu et al[8]
(Cu(DDC)2)	Inhibiting proteasome and leading to ER stress activation	Chen et al[9]
Copper ion chelating agent	Inhibiting endothelial cell proliferation and angiogenesis	Zhou et al[15]
Copper ion transporter inhibitor	Inhibit endothelial cell proliferation and angiogenesis	Yee et al[13], Karginova et al[14]
NPs(Cu-CysNPs)	Reacting with glutathione to increase ROS level	Ma et al[18]
Cu-TSC	Inducing ROS accumulation	Sîrbu et al[19]
Cu-NSAID compound	Inducing ROS accumulation, DNA damage and COX-2 activity inhibition	Boodram et al[20]
Copper complexes containing polypyridine ligands	Increasing ROS level and inducing ER stress	Kaur et al[21]

ROS: Reactive oxygen species; TSC: Tuberous sclerosis complex; COX-2: Cyclooxygenase-2; NSAID: Non-steroidal anti-inflammatory drugs; (Cu(DDC)2): Copper diethyldithiocarbamate; ER: Endoplasmic reticulum.

Table 2 Functions of cuproptosis-related genes in cancer

Genes	Mechanism	Ref.
FDX1	FDX1 knockout promotes glycolysis and fatty acid oxidation and alters amino acid metabolism	Zhang et al[26]
LIAS	Involved in lipoic acid biosynthesis. Abnormally elevated transcript levels of LIAS contribute to the development of lung cancer	Burr et al[29]
LIPT1	Participating in the tricarboxylic acid cycle and is related to the prognosis of bladder cancer	Solmonson et al[31], Chen et al[32]
DLD	Affecting pyruvate metabolism and tricarboxylic acid cycle. Leading to mitochondrial lipid peroxidation and is a potential targeted therapeutic molecule	Wang et al[33]
DLAT	Converting pyruvate to acetyl-COA Promoting cancer cell growth by activating pentose phosphate pathway	Shan et al[40]
PDHA1	Inhibition of PDHA1 expression promotes glycolysis and cell proliferation	Zhuang et al[43]
	PDHA1 promotes mitochondrial lipid synthesis	Chen et al[45]
PDHB	Overexpression of PDHB inhibits the proliferation and invasiveness	Zhu et al[46]
MTF1	Induced co-expression of metallothionein with other genes involved in metal homeostasis contributes to tumor biogenesis and development	Günther et al[51]
GLS	Encoding K-type mitochondrial glutaminase and is dysregulated in many tumors	Choi and Park[52], Momcilovic et al[53]
CDKN2A	A cyclin with mutations and aberrant methylation in a variety of tumors	Zhao et al[56], Tam et al[60]

FDX1: Ferredoxin 1; LIAS: Lipoic acid synthase; LIPT1: Lipoyltransferase 1; DLD: Dihydrolipoamide dehydrogenase; DLAT: Dihydrolipoamide transacetylase; PDHA1: Pyruvate dehydrogenase alpha 1; PDHB: Pyruvate dehydrogenase beta; MTF1: Metallothionein; GLS: Glutaminase; CDKN2A: Cyclin dependent kinase inhibitor 2A.