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表2 铜相关肿瘤治疗药物作用机制及其临床应用
Table 2 Mechanisms and clinical applications of copper⁃related tumor therapeutic drugs
Type of treatment Representative drug Core mechanism of action Research/clinical application
Copper chelators Trientine ①Chelates copper and promotes urinary ① Originally used for Wilson’s disease，with
excretion； lower toxicity than D⁃penicillamine；
② Inhibits IL ⁃ 8 and CD31 expression ②Exhibits anti⁃tumor effects on hepatocellular
and endothelial proliferation； carcinoma；
③ Inhibits angiogenesis to block tumor ③Combination therapy can inhibit tumor angio⁃
growth genesis in animal models
Copper chelators Tetrathiomolybdate ①Specifically chelates copper and forms ① Inhibits tumor growth and angiogenesis in
（TTM） insoluble complexes for excretion； multiple animal models；
②Inhibits NF⁃κB activity and HIF⁃1α，②Phase Ⅱ trials show delayed progression of
regulating copper transport； dermatofibrosarcoma protuberans，with poten⁃
③Upregulates CTR1 to enhance the cy⁃ tial for combination or adjuvant renal cancer
totoxicity of platinum⁃based chemothera⁃ therapy；
peutic agents ③ Enhances the efficacy of platinum ⁃ based
agents（e.g.，oxaliplatin）invarious cancer models
D ⁃ penicillamine（D ⁃ ① Chelates copper and other cations；① Originally a penicillin metabolite，used for
pen） thiol group mediates cytotoxicity； Wilson’s disease；
② Inhibits LOX activity and VEGF ex⁃ ② Slows glioblastoma progression；low ⁃ copper
pression； diet reduces tumor burden；

③ Downregulates ATP7A to reverse re⁃ ③Enhances oxaliplatin efficacy in cervical can⁃
sistance to platinum⁃based drugs cer
Copper ionopho ⁃ Disulfiram（DSF） ① Converts to DDTC in acidic environ⁃ ①Originally an alcohol deterrent；safe and pene⁃
res（inducing cu⁃ ments and chelates copper； trates the blood⁃brain barrier；
proptosis） ②Inhibits ALDH and NF⁃κB，producing ②Copper combination therapy effective against
ROS； multiple cancers；
+
③Targets and eliminates ALDH cancer ③ Combination with temozolomide prolongs
stem cells progression⁃free survival in glioblastoma
2+
Elesclomol ①Forms a 1∶1 complex with Cu ； ①Enhances taxane activity with good tolerance；
② Induces ROS production in tumor ②Phase Ⅱ：combination with taxane doubles
cells，triggering oxidative stress⁃induced progression⁃free survival in late⁃stage melano⁃
death； ma；
③ More sensitive to tumors dependent ③Phase Ⅲ：did not reach primary end point，
on mitochondrial metabolism but effective in specific populations
Copper complex⁃ Platinum⁃based anti⁃ Regulates copper transport/export pro⁃ ①Tumors acquire platinum resistance via cop⁃
es（chemical sen⁃ cancer drugs teins and copper chaperone function to per homeostasis mechanisms；
sitizers） improve platinum drug trafficking and ②Copper chelator combination with platinum⁃
overcome resistance based drugs overcomes resistance and improves
efficacy in ovarian cancer models
肿瘤模型（RIP1⁃Tag2 小鼠）中，TTM 可延缓癌前病 生成作用，可延缓Ⅰ/Ⅱ期患者疾病进展；虽单药治
变血管生成及晚期肿瘤生长；其作用机制包括减少 疗未改善肾癌患者生存率，但与其他抗血管生成药
VEGF、IL⁃1α 等下游因子分泌，诱导HIF⁃1α降解，抑 物联用或可提升疗效。

制 CCS 向 LOX 等铜酶的铜输送，还可影响 MEK1/2 4.3 铜离子载体
激酶活性，抑制 BRAFV600E 肿瘤异种移植生长。 铜对细胞生存增殖至关重要，但过量铜可通过
临床研究显示，TTM对恶性间皮瘤患者具有抗血管 产生 ROS 诱发毒性。部分癌症存在持续性氧化应