F-18-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis
文献类型：期刊论文
| 作者 | Jiang, Yuchen7,8; Zeng, Qinghe6; Jiang, Qinghui5,6; Peng, Xia7; Gao, Jing3,4; Wan, Haiyan7; Wang, Luting6; Gao, Yinglei7; Zhou, Xiaoyu6; Lin, Dongze7 |
| 刊名 | THERANOSTICS
 |
| 出版日期 | 2022 |
| 卷号 | 12期号:14页码:6395-6408 |
| 关键词 | F-18-FDG FGFR Therapeutic Response PET/CT mTOR/HK2 |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.74848 |
| 通讯作者 | Ding, Jian(jding@simm.ac.cn) ; Ai, Jing(jai@simm.ac.cn) ; Huang, Ruimin(rmhuang@simm.ac.cn) |
| 英文摘要 | Rationale: The overall clinical response to FGFR inhibitor (FGFRi) is far from satisfactory in cancer patients stratified by FGFR aberration, the current biomarker in clinical practice. A novel biomarker to evaluate the therapeutic response to FGFRi in a non-invasive and dynamic manner is thus greatly desired. Methods: Six FGFR-aberrant cancer cell lines were used, including four FGFRi-sensitive ones (NCI-H1581, NCI-H716, RT112 and Hep3B) and two FGFRi-resistant ones (primary for NCI-H2444 and acquired for NCI-H1581/AR). Cell viability and tumor xenograft growth analyses were performed to evaluate FGFRi sensitivities, accompanied by corresponding F-18-fluorodeoxyglucose (F-18-FDG) uptake assay. mTOR/PLCy/MEK-ERK signaling blockade by specific inhibitors or siRNAs was applied to determine the regulation mechanism. Results: FGFR inhibition decreased the in vitro accumulation of F-18-FDG only in four FGFRi-sensitive cell lines, but in neither of FGFRi-resistant ones. We then demonstrated that FGFRi-induced transcriptional downregulation of hexokinase 2 (HK2), a key factor of glucose metabolism and FDG trapping, via mTOR pathway leading to this decrease. Moreover, F-18-FDG PET imaging successfully differentiated the FGFRi-sensitive tumor xenografts from primary or acquired resistant ones by the tumor F-18-FDG accumulation change upon FGFRi treatment. Of note, both F-18-FDG tumor accumulation and HK2 expression could respond the administration/withdrawal of FGFRi in NCI-H1581 xenografts correspondingly. Conclusion: The novel association between the molecular mechanism (FGFR/mTOR/HK2 axis) and radiological phenotype (F-18-FDG PET uptake) of FGFR-targeted therapy was demonstrated in multiple preclinical models. The adoption of F-18-FDG PET biomarker-based imaging strategy to assess response/resistance to FGFR inhibition may benefit treatment selection for cancer patients. |
| WOS关键词 | METASTATIC CHOLANGIOCARCINOMA ; DOSE-ESCALATION ; OPEN-LABEL ; PHASE-I ; GROWTH ; INHIBITOR ; JNJ-42756493 ; ERDAFITINIB ; MULTICENTER ; MANAGEMENT |
| 资助项目 | National Natural Science Foundation of China[91859106] ; National Natural Science Foundation of China[82172001] ; National Natural Science Foundation of China[82173834] ; National Natural Science Foundation of China[81821005] ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02] ; Shanghai Science and Technology Committee[20S11901400] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000877381600022 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302885]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian; Ai, Jing; Huang, Ruimin |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Nucl Med, Shanghai 200092, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Analyt Res Ctr Organ & Biol Mol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Mol Imaging Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Nanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Yuchen,Zeng, Qinghe,Jiang, Qinghui,et al. F-18-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis[J]. THERANOSTICS,2022,12(14):6395-6408. |
| APA | Jiang, Yuchen.,Zeng, Qinghe.,Jiang, Qinghui.,Peng, Xia.,Gao, Jing.,...&Huang, Ruimin.(2022).F-18-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis.THERANOSTICS,12(14),6395-6408. |
| MLA | Jiang, Yuchen,et al."F-18-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis".THERANOSTICS 12.14(2022):6395-6408. |
入库方式： OAI收割
来源：上海药物研究所
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