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（续表2）
Clinical translational
Year Core discovery Key target Tumor type Resistance mechanism Reference
significance
2024 circCOL1A1 promotes circCOL1A1 Colorectal can⁃ Enhances glutamine catab⁃ circCOL1A1 as a prog⁃ ［24］
glutaminolysis through miR⁃214⁃3p， cer olism，provides energy and nostic marker，target⁃
the miR⁃ 214⁃3p/GLS1 GLS1 biosynthetic precursors，ing this axis can inhibit
axis promotes tumor prolifera⁃ tumor metabolism and
tion and metastasis progression
2025 The mitochondrial glu⁃ SLC1A5_var， Pancreatic can⁃ iMQT ⁃ 020 blocks mito⁃ Highly selective and ［31］
tamine transporter iMQT ⁃ 020（al⁃ cer，lung can⁃ chondrial glutamine up⁃ low ⁃ toxicity metabolic
SLC1A5_var and its losteric inhibi⁃ cer，breast can⁃ take，leading to TCA cycle inhibitor， synergistic
allosteric inhibitor tory site） cer，and multi⁃ impairment，reduced GSH with PD⁃1/PD⁃L1 anti⁃
iMQT⁃020 achieve spa⁃ ple solid tu⁃ synthesis，and ROS accu⁃ bodies，providing a new
tially specific targeting mors mulation，triggering energy strategy to overcome
of tumor glutamine me⁃ crisis and oxidative stress，GLS inhibitor resis⁃
tabolismforthe first time and inducing tumor cell tance
death

（表 3）。再者，肿瘤细胞具有高度的异质性和适应 克的重点。
性，在针对Gln代谢进行治疗时，肿瘤细胞可能会通 此外，Gln 代谢的复杂性也提示单一靶点的干
过其他代谢途径的代偿来维持生存和增殖，如何全 预可能难以取得理想的治疗效果，联合治疗策略的
面阻断肿瘤的代谢逃逸途径也是未来研究需要攻 开发显得尤为重要。总之，Gln 代谢在肿瘤耐药中

表3 Gln代谢靶向药物临床转化现状（按靶点类型分类）
Table 3 Clinical translation status of glutamine metabolism⁃targeted drugs（classified by target type）
Representative Development
Target type Clinical trial result Core failure reason Reference
drug stage
Transporter V⁃9302（SLC1A5 Preclinical Showed antitumor activity in Lack of target specificity：simultane⁃ ［61］
inhibitor inhibitor） （discontinued） preclinical studies，but efficacy ously inhibits multiple amino acid
was not related to SLC1A5 inhi⁃ transporters；significant off⁃target ef⁃
bition fects
iMQT⁃020 Preclinical op⁃ Pancreatic cancer model：75% Not yet entered clinical validation ［31］
（SLC1A5_var，mi⁃ timization stage tumor suppression，40% CR
tochondria ⁃ spec ⁃ rate when combined with PD⁃1，
ific） high selectivity，low toxicity

Metabolic CB⁃839（GLS1 in⁃ Phase Ⅱ（dis⁃ RCC combined with everolim⁃ ① Metabolic compensation：FAO ［62］
enzyme in⁃ hibitor） continued） us：PFS HR=0.83（P=0.29）；↑ ，glycolysis ↑ ，SLC7A11 ⁃ GSH
hibitor TNBC and CRC did not meet loop activation；② Lack of biomark⁃
endpoints； monotherapy in ers：did not screen for MYC/LKB1⁃
NSCLC failed high expression population；③ Nor⁃
mal tissue toxicity：high GLS1 ex⁃
pression in intestine/kidney

BPTES（GLS1 in⁃ Preclinical Poor water solubility，poor phar⁃ Physicochemical property limita⁃ ［63］
hibitor） （discontinued） macokinetics， did not enter tions：poor druggability，low bio⁃
clinic availability
Combination CB⁃839 + Evero⁃ Phase Ⅱ（par⁃ TNBC：significantly inhibited Combination strategy relatively suc⁃ ［64］
regimen limus tially positive） tumor proliferation，overcame cessful
monotherapy resistance