徐瑞华

徐瑞华，中国医学科学院学术咨询委员会学部委员，中山大学肿瘤防治中心主任、医院院长、研究所所长，华南恶性肿瘤防治全国重点实验室主任，教授，博士生导师。

兼任中国临床肿瘤学会理事长，中国抗癌协会副理事长，中国抗癌协会靶向治疗专委会首届主任委员、化疗专委会候任主任委员，中国临床肿瘤学会肠癌专委会主任委员、胃癌专委会首届主任委员，《Cancer Communications》（IF 20.1）主编，研究生教材《肿瘤学》及本科生教材《临床肿瘤学》主编。

以第一完成人获得国家科技进步二等奖2项，中华医学科技奖、教育部科技奖及广东省科技奖一等奖共6项。获得第三届全国创新争先奖、何梁何利基金科学与技术奖、谈家桢临床医学奖、吴阶平医学创新奖以及中国临床肿瘤学会年度成就奖。获中国医院协会优秀院长称号。入选国家百千万人才工程、南粤百杰人才工程等，获国家卫健委突出贡献中青年专家、全国先进工作者、全国五一劳动奖状及享受国务院特殊津贴专家。以最后通讯作者（含少量共同通讯）在JAMA（2篇）、BMJ、Cell、Nature Med（5篇）、Nature Mater、Lancet Oncol（2篇）、Cancer Cell（3篇）、Ann Oncol(2篇)、JCO（2篇）、Lancet G&H（2篇）、JAMA Oncol（2篇） 等发表高水平成果论文200 余篇（30篇IF>30），成果被写入57部国际指南，连续2年入选科睿唯安（Clarivate）全球高被引科学家，连续7年入选中国高被引学者榜单，H指数85。获创新药物等24项专利授权，转化5 项。牵头制定了《中国临床肿瘤学会结直肠癌诊疗指南》等15本诊疗指南规范。

从事肿瘤内科临床及科研工作36年，是一位典型的临床医学科学家，取得突破性成果。

（一）建立了结直肠癌诊治新体系，使我国肠癌精准诊治均处于国际先进水平

创新了肠癌早诊及疗效预测的新技术，提高了诊断和预测的效率，并已转化为临床应用，其中一项试剂盒已获得国家NMPA医疗器械注册批准。

改变了局部晚期直肠癌根治模式，首创了新辅助免疫药物根治方案（完全缓解率达75%），使dMMR类型患者（约占5%）免于放化疗、手术和人工肛；建立了免疫联合放化疗的术前方案，使pMMR 类型患者（占95%）近期肿瘤治愈率及豁免手术率明显提高。

丰富和发展了国际晚期肠癌治疗体系，首创了高效低毒的维持方案、亚洲方案及靶向方案，成为国际治疗新标准；基于免疫微环境研究，创建了组蛋白去乙酰化酶抑制剂+靶向+免疫药物的中国CAP方案，疗效大幅度提高。

通过体系创新，晚期肠癌生存期提高了3倍，与美国安德森癌症中心达相同水平，部分晚期转移患者获得治愈。

（二）创新了上消化道肿瘤免疫治疗范式，达国际领先水平

通过鉴定新型标志物，精准筛选免疫治疗敏感亚型，大幅提高PD-1抗体疗效；首创了食管癌中国免疫联合方案，取得全球最高有效率72%，已成为食管癌治疗应用最广泛的方案；建立了食管癌EGIC分型，可以指导精准免疫治疗策略，引领该领域的发展；作为两项胃癌研究的全球首席科学家，创建了新免疫靶点CLDN18.2抗体联合新方案治疗晚期胃癌，及PD-1抗体免疫联合新方案，明显降低了死亡风险，成为两个全球新方案；进一步把免疫新方案应用到可手术胃癌患者，大幅提高了近期治愈率。首创免疫治疗药物肠道活性菌RX-af01，成果已获得专利并已产业转化，正在进行新药临床报批。

此外，还牵头负责了多个国产创新药临床研究，推动这些创新药物在我国上市，解决新药“卡脖子”问题，间接产生的价值超百亿元。负责的多项临床研究，得到欧洲、美国药监局的高度评价及批准，开创了我国自主研发的生物单抗创新药物及其新联合方案走向欧美等国家的先河。

Representative paper:

1. Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH#  ESCORT-1st Investigators.  Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925.
2. Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW, Wang J, Poddubskaya E, Pan H, Rha SY, Zhang R, Hirano H, Spigel D, Yamaguchi K, Chao Y, Wyrwicz L, Disel U, Cid RP, Fornaro L, Evesque L, Wang H, Xu Y, Li J, Sheng T, Yang S, Li L, Moehler M, Xu RH#; RATIONALE-305 Investigators. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024 May 28;385:e078876.
3. Manish A Shah, Kohei Shitara, Jaffer A Ajani, Yung-Jue Bang, Peter Enzinger, David Ilson, Florian Lordick, Eric Van Cutsem, Javier Gallego Plazas, Jing Huang, Lin Shen, Sang Cheul Oh, Patrapim Sunpaweravong, Hwoei Fen Soo Hoo, Haci Mehmet Turk, Mok Oh, Jung Wook Park, Diarmuid Moran, Pranob Bhattacharya, Ahsan Arozullah, Rui-Hua Xu#. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141.
4. Wang F, Shen L, Guo W, Liu T, Li J, Qin S, Bai Y, Chen Z, Wang J, Pan Y, Shu Y, Zhao F, Cheng Y, Ye F, Gu K, Zhang T, Pan H, Zhong H, Zhou F, Qin Y, Yang L, Mao W, Li Q, Dai W, Li W, Wang S, Tang Y, Ma D, Yin X, Deng Y, Yuan Y, Li M, Hu W, Chen D, Li G, Liu Q, Tan P, Fan S, Shi M, Su W, Xu RH#. Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial. Nat Med. 2024 Jun 1. Epub ahead of print.
5. Wang F, Jin Y, Wang M, Luo HY, Fang WJ, Wang YN, Chen YX, Huang RJ, Guan WL, Li JB, Li YH, Wang FH, Hu XH, Zhang YQ, Qiu MZ, Liu LL, Wang ZX, Ren C, Wang DS, Zhang DS, Wang ZQ, Liao WT, Tian L, Zhao Q, Xu RH#. Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial. Nat Med. 2024 Apr;30(4):1035-1043.
6. Yuan SQ, Nie RC, Jin Y, Liang CC, Li YF, Jian R, Sun XW, Chen YB, Guan WL, Wang ZX, Qiu HB, Wang W, Chen S, Zhang DS, Ling YH, Xi SY, Cai MY, Huang CY, Yang QX, Liu ZM, Guan YX, Chen YM, Li JB, Tang XW, Peng JS, Zhou ZW, Xu RH#, Wang F. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial. Nat Med. 2024 Feb;30(2):552-559. doi: 10.1038/s41591-023-02721-w. Epub 2024 Jan 2. Erratum in: Nat Med. 2024 Feb;30(2):605.
7. Xu RH#, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu JK, Hao X and Zhang K. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017 Nov;16(11):1155-1161.
8. Xu RH#, Muro K, Morita S, Iwasa S, Han SW, Wang W, Kotaka M, Nakamura M, Ahn JB, Deng YH, Kato T, Cho SH, Ba Y, Matsuoka H, Lee KW, Zhang T, Yamada Y, Sakamoto J, Park YS and Kim TW. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol 2018 May;19(5):660-671.
9. Luo H, Xu G, Li C, He L, Luo L, Wang Z, Jing B, Deng Y, Jin Y, Li Y, Li B, Tan W, He C, Seeruttun SR, Wu Q, Huang J, Huang DW, Chen B, Lin SB, Chen QM, Yuan CM, Chen HX, Pu HY, Zhou F, He Y, Xu RH#. Real-time artificial intelligence for detection of upper gastrointestinal cancer by endoscopy: a multicentre, case-control, diagnostic study. Lancet Oncol. 2019 Dec;20(12):1645-1654.
10. Xiao WW, Chen G, Gao YH, Lin JZ, Wu XJ, Luo HL, Lu ZH, Wang QX, Sun R, Cai PQ, Zhu CM, Liu M, Li JB, Wang YR, Jin Y, Wang F, Luo HT, Li CL, Pan ZZ, Xu RH#. Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial. Cancer Cell. 2024 Jul 24:S1535-6108(24)00269-1.Epub ahead of print.
11. Yan-Xing Chen, Zi-Xian Wang, Ying Jin, Qi Zhao, Ze-Xian Liu, Zhi-Xiang Zuo, Huai-Qiang Ju, Chengxu Cui, Jun Yao, Yanqiao Zhang, Mengxia Li, Jifeng Feng, Lin Tian, Xiao-Jun Xia, Hui Feng, Sheng Yao, Feng-Hua Wang, Yu-Hong Li, Feng Wang, Rui-Hua Xu#. An immunogenic and oncogenic feature-based classification for chemotherapy plus PD-1 blockade in advanced esophageal squamous cell carcinoma. Cancer Cell. 2023 May 8;41(5):919-932.e5.
12. Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L, Shu Y, Wang C, Dai T, Mao T, Chen L, Guo Z, Liu B, Pan H, Cang S, Jiang Y, Wang J, Ye M, Chen Z, Jiang D, Lin Q, Ren W, Wang J, Wu L, Xu Y, Miao Z, Sun M, Xie C, Liu Y, Wang Q, Zhao L, Li Q, Huang C, Jiang K, Yang K, Li D, Liu Y, Zhu Z, Chen R, Jia L, Li W, Liao W, Liu HX, Ma D, Ma J, Qin Y, Shi Z, Wei Q, Xiao K, Zhang Y, Zhang Y, Chen X, Dai G, He J, Li J, Li G, Liu Y, Liu Z, Yuan X, Zhang J, Fu Z, He Y, Ju F, Liu Z, Tang P, Wang T, Wang W, Zhang J, Luo X, Tang X, May R, Feng H, Yao S, Keegan P, Xu RH#, Wang F. Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer Cell. 2022 Mar 14;40(3):277-288.
13. Wu HX, Pan YQ, He Y, Wang ZX, Guan WL, Chen YX, Yao YC, Shao NY, Xu RH#, Wang F. Clinical Benefit of First-Line Programmed Death-1 Antibody Plus Chemotherapy in Low Programmed Cell Death Ligand 1-Expressing Esophageal Squamous Cell Carcinoma: A Post Hoc Analysis of JUPITER-06 and Meta-Analysis. J Clin Oncol. 2023 Mar 20;41(9):1735-1746.
14. Wang FH, Wei XL, Feng J, Li Q, Xu N, Hu XC, Liao W, Jiang Y, Lin XY, Zhang QY, Yuan XL, Huang HX, Chen Y, Dai GH, Shi JH, Shen L, Yang SJ, Shu YQ, Liu YP, Wang W, Wu H, Feng H, Yao S, Xu RH#. Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). J Clin Oncol. 2021 Mar 1;39(7):704-712.
15. Luo HY, Li YH, Wang W, Wang ZQ, Yuan X, Ma D, Wang FH, Zhang DS, Lin DR, Lin YC, Jia J, Hu XH, Peng JW and Xu RH#. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol. 2016 Jun;27(6):1074-1081. 
16. Wang F, Wei XL, Wang FH, Xu N, Shen L, Dai GH, Yuan XL, Chen Y, Yang SJ, Shi JH, Hu XC, Lin XY, Zhang QY, JF Feng, Y Ba, YP Liu, W Li, YQ Shu, Y Jiang, Q Li, JW Wang, H Wu, H Feng, S Yao, RH Xu#. Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432. Ann Oncol. 2019 Sep 1;30(9):1479-1486.
17. Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, Xu RH#. Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types. JAMA Oncol. 2019 Oct 1;5(10):1513. 
18. Qiu MZ, Zhang Y, Guo Y, Guo W, Nian W, Liao W, Xu Z, Zhang W, Zhao HY, Wei X, Xue L, Tang W, Wu Y, Ren G, Wang L, Xi J, Jin Y, Li H, Hu C, Xu RH#. Evaluation of Safety of Treatment With Anti-Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1042-1046.
19. Chen G, Jin Y, Guan WL, Zhang RX, Xiao WW, Cai PQ, Liu M, Lin JZ, Wang FL, Li C, Quan TT, Xi SY, Zhang HZ, Pan ZZ, Wang F, Xu RH#. Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study. Lancet Gastroenterol Hepatol. 2023 May;8(5):422-431.
20. Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024.
21. Rui-Hua Xu, Jin Li, Yuxian Bai, Jianming Xu, Tianshu Liu, Lin Shen, Liwei Wang, Hongming Pan, Junning Cao, Dongsheng Zhang, Songhua Fan, Ye Hua & Weiguo Su. Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. J Hematol Oncol. 2017 Jan 19;10(1):22.
22. Gong Chen, Junjie Peng, Qian Xiao, Hao-Xiang Wu, Xiaojun Wu, Fulong Wang, Liren Li, Peirong Ding, Qi Zhao, Yaqi Li, Da Wang, Yang Shao, Hua Bao, Zhizhong Pan, Ke-Feng Ding, Sanjun Cai, Feng Wang, Rui-Hua Xu#. Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. J Hematol Oncol. 2021 May 17;14(1):80.
23. Wang F, Liu DB, Zhao Q, Chen G, Liu XM, Wang YN, Su H, Qin YR, He YF, Zou QF, Liu YH, Lin YE, Liu ZX, Bei JX and Xu RH#. The genomic landscape of small cell carcinoma of the esophagus. Cell Res 2018 Jul;28(7):771-774.
24. Wang DS, Liu ZX, Lu YX, Bao H, Wu X, Zeng ZL, Liu Z, Zhao Q, He CY, Lu JH, Wang ZQ, Qiu MZ, Wang F, Wang FH, Li YH, Wang XN, Xie D, Jia WH, Shao YW and Xu RH#. Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer. Gut 2019 Jul;68(7):1152-1161.
25. Li T, Tan YT, Chen YX, Zheng XJ, Wang W, Liao K, Mo HY, Lin J, Yang W, Piao HL, Xu RH#, Ju HQ. Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. Gut. 2023 Mar;72(3):501-511.
26. Feng Wang, You-Sheng Huang, Hao-Xiang Wu, Zi-Xian Wang, Ying Jin, Yi-Chen Yao, Yan-Xing Chen, Qi Zhao, Shifu Chen, Ming-Ming He, Hui-Yan Luo, Miao-Zhen Qiu, De-Shen Wang, Feng-Hua Wang, Mingyan Xu, Yu-Hong Li, Rui-Hua Xu#. Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment. Gut. 2022 Jul;71(7):1340-1349.
27. Yi Han, Yan-Yu Zhang, Yi-Qian Pan, Xiao-Jun Zheng, Kun Liao, Hai-Yu Mo, Hui Sheng, Qi-Nian Wu, Ze-Xian Liu, Zhao-Lei Zeng, Wei Yang, Shu-Qiang Yuan, Peng Huang, Huai-Qiang Ju, Rui-Hua Xu#. IL-1β-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance. Mol Cell. 2023 Jun 1;83(11):1887-1902.e8.
28. Qiu MZ, Wang C, Wu Z, Zhao Q, Zhao Z, Huang CY, Wu W, Yang LQ, Zhou ZW, Zheng Y, Pan HM, Liu Z, Zeng ZL, Luo HY, Wang F, Wang FH, Yang SY, Huang MX, Lian Z, Zhang H, Xu RH#. Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response. Signal Transduct Target Ther. 2023 Sep 21;8(1):370.  
29. Zheng-Yu Qian, Yi-Qian Pan, Xue-Xin Li, Yan-Xing Chen, Hao-Xiang Wu, Ze-Xian Liu, Martin Kosar, Jiri Bartek, Zi-Xian Wang, Rui-Hua Xu#. Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy. Sci Bull (Beijing). 2024 Mar 30;69(6):803-822. 
30. Zhao Q, Wang F, Chen YX, Chen S, Yao YC, Zeng ZL, Jiang TJ, Wang YN, Wu CY, Jing Y, Huang YS, Zhang J, Wang ZX, He MM, Pu HY, Mai ZJ, Wu QN, Long R, Zhang X, Huang T, Xu M, Qiu MZ, Luo HY, Li YH, Zhang DS, Jia WH, Chen G, Ding PR, Li LR, Lu ZH, Pan ZZ, Xu RH#. Comprehensive profiling of 1015 patients' exomes reveals genomic-clinical associations in colorectal cancer. Nat Commun. 2022 Apr 29;13(1):2342.

更新时间：2024年8月15日