Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.
Xingbin HuZhenfeng MaBeibei XuShulong LiZhiqi YaoBishan LiangJiao WangWang-Jun LiaoLi LinChunling WangSiting ZhengQijing WuQiong HuangLe YuFeng-Hua WangMin ShiPublished in: Cancer communications (London, England) (2023)
This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro-angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2-positive gastric cancer. A combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.