Biography

• QIN Wenxin obtained his BSc degree in Biochemistry from Wuhan University in 1985, MSc degree in Medical Science from Medical College of Soochow University in 1994, and PhD degree in Medical Science from Shanghai Medical College of Fudan University in 1998. He was a visiting scholar at Institute for Systems Biology, Seattle, USA during 2007-2008.

• His lab mainly focuses on molecular mechanisms of cancer, tumor microenvironment, and novel diagnostic and therapeutic strategies for cancer. This lab found that the secreted protein DKK1 was highly expressed in hepatocellular carcinoma. The results from phase II multicenter clinical trial of biomarker showed that DKK1 could be used as a diagnosis marker for early hepatocellular carcinoma and hepatocellular carcinoma with alpha fetoprotein (AFP) negative. Combining DKK1 with AFP could significantly improve the diagnostic ability for HCC (The Lancet Oncology 2012). His lab also demonstrated for the first time that RCAN1 isoform 4 (RCAN1.4) acts as a novel suppressor of HCC through regulation of the calcineurin-nuclear factor of activated T cells pathway (Gastroenterology 2017). Using a kinome-focused CRISPR-Cas9 genetic screen, his lab and collaborators showed that pharmacological inhibition of the DNA-replication kinase CDC7 induced senescence selectively in liver cancer cells with mutations in TP53. A chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. The results experimentally validated the one–two punch therapy for treatment of liver cancer with mutations in TP53 (Nature 2019). His lab and collaborators also found that inhibition of epidermal growth factor receptor (EGFR) was synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displayed potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. This combination therapy identified may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR (Nature 2021).

Selected Publications

1. Yu B, Yang X, Xu Y, Yao G, Shu H, Lin B, Hood L, Wang H, Yang S, Gu J, Fan J*, Qin W*. Elevated expression of DKK1 is associated with cytoplasmic/nuclear beta-catenin accumulation and poor prognosis in hepatocellular carcinomas. J Hepatol. 2009 May;50(5):948-57.

2. Shen Q, Fan J, Yang XR, Tan Y, Zhao W, Xu Y, Wang N, Niu Y, Wu Z, Zhou J, Qiu SJ, Shi YH, Yu B, Tang N, Chu W, Wang M, Wu J, Zhang Z, Yang S, Gu J, Wang H, Qin W*. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncology 2012;13(8):817-26.

3. Jin H, Wang C, Jin G, Ruan H, Gu D, Wei L, Wang H, Wang N, Arunachalam E, Zhang Y, Deng X, Yang C, Xiong Y, Feng H, Yao M, Fang J, Gu J, Cong W*, Qin W*. Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1. Gastroenterology 2017 Sep;153(3):799-811.

4. Cheng Z, Yu C, Cui S, Wang H, Jin H, Wang C, Li B, Qin M, Yang C, He J, Zuo Q, Wang S, Liu J, Ye W, Lv Y, Zhao F, Yao M, Jiang L*, Qin W*. circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1. Nat Commun. 2019 Jul 19;10(1):3200.

5. Wang C, Vegna S, Jin H, Benedict B, Lieftink C, Ramirez C, de Oliveira RL, Morris B, Gadiot J, Wang W, du Chatinier A, Wang L, Gao D, Evers B, Jin G, Xue Z, Schepers A, Jochems F, Sanchez AM, Mainardi S, TeRiele H, Beijersbergen RL, Qin W*, Akkari L*, Bernards R*. Inducing and exploiting vulnerabilities for the treatment of liver cancer. Nature 2019 Oct;574(7777):268-272.

6. Yu C, Cheng Z, Cui S, Mao X, Li B, Fu Y, Wang H, Jin H, Ye Q, Zhao X, Jiang L*, Qin W*. circFOXM1 promotes proliferation of non-small cell lung carcinoma cells by acting as a ceRNA to upregulate FAM83D. J Exp Clin Cancer Res. 2020 Mar 30;39(1):55.

7. Zuo Q, He J, Zhang S, Wang H, Jin G, Jin H, Cheng Z, Tao X, Yu C, Li B, Yang C, Wang S, Lv Y, Zhao F, Yao M, Cong W, Wang C*, Qin W*. PGC1α suppresses metastasis of HCC by inhibiting Warburg effect via PPARγ-dependent WNT/β-catenin/PDK1 axis. Hepatology 2021 Feb;73(2):644-660.

8. Li B, Zhu L, Lu C, Wang C, Wang H, Jin H, Ma X, Cheng Z, Yu C, Wang S, Zuo Q, Zhou Y, Wang J, Yang C, Lv Y, Jiang L*, Qin W*. circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun. 2021 Jan 12;12(1):295.

9. Jin H, Shi Y, Lv Y, Yuan S, Ramirez CFA, Lieftink C, Wang L, Wang S, Wang C, Dias MH, Jochems F, Yang Y, Bosma A, Hijmans EM, de Groot MHP, Vegna S, Cui D, Zhou Y, Ling J, Wang H, Guo Y, Zheng X, Isima N, Wu H, Sun C, Beijersbergen RL, Akkari L, Zhou W*, Zhai B*, Qin W*, Bernards R*. EGFR activation limits the response of liver cancer to lenvatinib. Nature. 2021 Jul;595(7869):730-734 (cover article).

10. Wang C*, Cao Y, Yang C, Bernards R*, Qin W*. Exploring liver cancer biology through functional genetic screens. Nat Rev Gastroenterol Hepatol. 2021 Oct;18(10):690-704. Review.