Xiaoyu Chen
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Xiaoyu Chen has a total of 11 co-authors. Here are the top co-authors by number of shared publications:
- David Wai Chan
Department of Obstetrics & Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
1 shared publication - Huijuan Wang
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
1 shared publication - Huogang Wang
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
1 shared publication - Jiawei Wang
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
1 shared publication - Jiaxin Chen
Department of Breast Surgery and Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
1 shared publication - Qing Meng
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
1 shared publication
Latest Publications
- Open Access
- 21 October 2024
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 134 (24)
MOGAT3-mediated DAG accumulation drives acquired resistance to anti-BRAF/anti-EGFR therapy in BRAFV600E-mutant metastatic colorectal cancer
BRAF V600E -mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis. The combination of anti-BRAF/anti-EGFR (encorafenib/cetuximab) treatment for patients with BRAF V600E -mutant mCRC improves clinical benefits; unfortunately, inevitable acquired resistance limits the treatment outcome, and the mechanism has not been validated. Here, we discovered that monoacylglycerol O-acyltransferase 3–mediated (MOGAT3-mediated) diacylglycerol (DAG) accumulation contributed to acquired resistance to encorafenib/cetuximab by dissecting a BRAF V600E -mutant mCRC patient–derived xenograft (PDX) model exposed to encorafenib/cetuximab administration. Mechanistically, the upregulated MOGAT3 promoted DAG synthesis and reduced fatty acid oxidation–promoting DAG accumulation and activated PKCα/CRAF/MEK/ERK signaling, driving acquired resistance. Resistance-induced hypoxia promoted MOGAT3 transcriptional elevation; simultaneously, MOGAT3-mediated DAG accumulation increased HIF1A expression at the translation level through PKCα/CRAF/eIF4E activation, strengthening the resistance status. Intriguingly, reducing intratumoral DAG with fenofibrate or PF-06471553 restored the antitumor efficacy of encorafenib/cetuximab in resistant BRAF V600E -mutant mCRC, which interrupted PKCα/CRAF/MEK/ERK signaling. These findings reveal the critical role of the metabolite DAG as a modulator of encorafenib/cetuximab efficacy in BRAF V600E -mutant mCRC, suggesting that fenofibrate might prove beneficial for resistant BRAF V600E -mutant mCRC patients.
- 21 October 2024
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 134 (24)
Open AccessMOGAT3-mediated DAG accumulation drives acquired resistance to anti-BRAF/anti-EGFR therapy in BRAFV600E-mutant metastatic colorectal cancer
BRAF V600E -mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis. The combination of anti-BRAF/anti-EGFR (encorafenib/cetuximab) treatment for patients with BRAF V600E -mutant mCRC improves clinical benefits; unfortunately, inevitable acquired resistance limits the treatment outcome, and the mechanism has not been validated. Here, we discovered that monoacylglycerol O-acyltransferase 3–mediated (MOGAT3-mediated) diacylglycerol (DAG) accumulation contributed to acquired resistance to encorafenib/cetuximab by dissecting a BRAF V600E -mutant mCRC patient–derived xenograft (PDX) model exposed to encorafenib/cetuximab administration. Mechanistically, the upregulated MOGAT3 promoted DAG synthesis and reduced fatty acid oxidation–promoting DAG accumulation and activated PKCα/CRAF/MEK/ERK signaling, driving acquired resistance. Resistance-induced hypoxia promoted MOGAT3 transcriptional elevation; simultaneously, MOGAT3-mediated DAG accumulation increased HIF1A expression at the translation level through PKCα/CRAF/eIF4E activation, strengthening the resistance status. Intriguingly, reducing intratumoral DAG with fenofibrate or PF-06471553 restored the antitumor efficacy of encorafenib/cetuximab in resistant BRAF V600E -mutant mCRC, which interrupted PKCα/CRAF/MEK/ERK signaling. These findings reveal the critical role of the metabolite DAG as a modulator of encorafenib/cetuximab efficacy in BRAF V600E -mutant mCRC, suggesting that fenofibrate might prove beneficial for resistant BRAF V600E -mutant mCRC patients.