代谢组学挖掘胆固醇在三阴性乳腺癌中的作用研究进展

Research Progress on Cholesterol in Triple Negative Breast Cancer Based on Metabonomics

近年来通过对三阴性乳腺癌(triple-negative breast cancer,TNBC)分子特征的研究发现其基因和代谢特征与其他类型显著不同,而且TNBC本身也由不同的亚型组成,TNBC的胆固醇合成以及代谢会增强,但不会大量积累胆固醇,而是增加对肿瘤生长有促进作用的代谢产物。全文分析胆固醇合成代谢过程中影响TNBC肿瘤微环境的关键分子机制。谷氨酰胺酶抑制剂、PI3K抑制剂临床前实验已得到良好疗效正在进行临床研究。神经鞘氨醇激酶抑制剂、mTOR抑制剂、STAT3抑制剂和RORγ拮抗剂都有可能成为TNBC新药研制的基础。总之,针对TNBC不同代谢亚型挖掘精准治疗手段非常有希望。

Recent studies have revealed that triple negative breast cancer(TNBC)has unique genetic and metabolic characteristics,and the synthesis and metabolism of cholesterol in TNBC are enhanced.However,the large amount of cholesterol synthesized by TNBC cells was not accumulated,but increase metabolites to promote tumor growth.The key molecular mechanisms affecting the microenvironment of TNBC during cholesterol anabolism are summarized in this article.The glutaminase inhibitors and PI3K inhibitors have achieved optimistic results in pre-clinical studies and are now undergoing clinical trials.Schmosine kinase inhibitor,m TOR inhibitor,STAT3 inhibitors and RORγantagonists are potential candidates for developing new anti-TNBC drugs.In conclusion,it is very promising to explore precise treatment for different metabolic subtypes of TNBC.