Page 149 - 南京医科大学自然版

第46卷第10期 陈奕文，张静静，张雄飞. 谷氨酰胺代谢和肿瘤耐药机制研究进展［J］.
2026年10月 南京医科大学学报（自然科学版），2026，46（10）：1567-1583 ·1579 ·

表2 谷氨酰胺代谢与肿瘤耐药相关重大研究进展（2020-2025）
Table 2 Major research advances in glutamine metabolism and tumor drug resistance（2020-2025）

Clinical translational
Year Core discovery Key target Tumor type Resistance mechanism Reference
significance
2020 SLC25A22 ⁃ mediated SLC25A22， Colorectal can⁃ Succinate accumulation in⁃ Suggests that combined ［48］
glutamine metabolism succinate，Wnt cer duces DNA hypermethyl⁃ metabolic intervention
promotes 5 ⁃ FU resis⁃ pathway ation，activates Wnt signal⁃ with epigenetic drugs
tance in KRAS ⁃ mutant ing，and enhances stem⁃ can reverse resistance
colorectal cancer ness properties
2021 SLC7A11 in KRAS⁃mu⁃ SLC7A11，GSH Pancreatic can⁃ High SLC7A11 expression First validation of the ［36］
tant pancreatic cancer ⁃GPX4 cer promotes cystine uptake，SLC7A11⁃GSH axis re⁃
resists ferroptosis in⁃ maintains GSH synthesis，sistance mechanism in
duction by maintaining inhibits lipid peroxidation，KRAS⁃mutant tumors
GSH synthesis resists ferroptosis，leading
to resistance to ferroptosis
inducers in KRAS⁃mutant
pancreatic cancer
2021 SLC1A5 upregulation SLC1A5，HIF ⁃ Pancreatic can⁃ Glutamine ⁃ dependent Suggests targeting ［30］
by HIF⁃2α in pancreatic 2α cer ATP and GSH synthesis SLC1A5 variants or
cancer enhances gluta⁃ enhanced，antioxidant ca⁃ combining with HIF⁃2α
mine uptake and gem⁃ pacity and energy supply inhibitors
citabine resistance
2022 Apatinib induces ami⁃ ATF4， Non ⁃ small cell Apatinib induces amino Combined inhibition of ［1］
no acid imbalance and SLC1A5， lung cancer acid metabolic imbalance，ATF4 reverses resis⁃
activates ATF4 to re⁃ ASNS， GCN2/ activates the GCN2/eIF2α/ tance，providing a new
program glutamine me⁃ eIF2α ATF4 amino acid stress re⁃ strategy to overcome tar⁃
tabolism，leading to re⁃ sponse pathway，upregu⁃ geted therapy resistance
sistance lates SLC1A5 and ASNS
expression，promotes gluta⁃
mine uptake and metabo⁃
lism，forming adaptive re⁃
sistance
2023 First discovery of the SLC38A5， Pancreatic can⁃ SLC38A5 mediates gluta⁃ SLC38A5 as a novel ［38］
important role of GSH， PI3K/ cer，breast can⁃ mine uptake，inhibits fer⁃ metabolic target and re⁃
SLC38A5 as a novel AKT/mTOR ⁃ cer，and multi⁃ roptosis through GSH syn⁃ sistance marker，provid⁃
glutamine transporter SREBP1⁃SCD1 ple tumors thesis antioxidant or PI3K/ ing precision interven⁃
in tumor resistance AKT/mTOR ⁃ SREBP1 ⁃ tion strategies for che⁃
SCD1 axis，promoting che⁃ motherapy resistance in
motherapy resistance pancreatic cancer，
breast cancer，etc.

2023 CAF ⁃ tumor cell gluta⁃ CAF，GS， Breast cancer，CAFs highly express GS to First systematic elucida⁃ ［43］
mine metabolic cou⁃ SLC1A5 pancreatic can⁃ catalyze glutamine synthe⁃ tion of the microenviron⁃
pling：CAF ⁃ secreted cer sis and transport it to tu⁃ ment metabolic cou⁃
glutamine supports tu⁃ mor cells，promoting their pling resistance mecha⁃
mor cell survival and glutamine⁃addictedmetabo⁃ nism，providing a basis
promotes resistance lism and enhancing che⁃ for targeting CAF
motherapy resistance