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- Research Projects
- JingXuan Pan
Professor of Medicine Director, Tissue Bank State Key Laboratory of Ophthalmology Sun Yat-sen University Zhongshan Ophthalmic Center; Principal Investigator, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China
54 South Xianlie Road, Guangzhou, China
- Clinical and Basical Research：Dr. Pan has been the principal investigator for several research projects supported by grants from National Natural Science Funds for Distinguished Young Scholars, the Major Research Plan of the National Natural Science Fund of China, the National Basic Research Program of China (973 Program), and the National High Technology Research and Development Program of China (863 Program grant). I have authored 45 articles published in international peer-reviewed journals including JNCI, Blood, Cancer Res, Clin Cancer Res, Leukemia, Mol Cancer Thera.
Email : email@example.com
- Research Projects
The research of Dr. Jingxuan Pan is in the areas of tumor pharmacology and ocular tumor. His major research interests are to validate novel molecular targets in tumor cells, develop novel and specific therapeutic agents and elucidate the mechanisms of drug action, particularly of small molecule tyrosine kinase inhibitors. Successful translating Gleevec (STI571, imatinib) to therapy of chronic myelogenous leukemia opened a new era of targeted therapeutics for cancer. However, resistance to Gleevec develops over time which is an emerging problem for patients with chronic myelogenous leukemia. Acquired point mutations within the target genes encoding tyrosine kinases (e.g. Bcr-Abl, KIT and PDGFRα) are a major mechanism of resistance to Gleevec in some patients with hematologic malignance. The mutations are believed to block the binding of Gleevec to ATP binding pockets of these tyrosine kinases. In this case, novel tyrosine kinase inhibitors such as nilotinib and dasatinib (also called the second-generation of tyrosine kinase inhibitor) have been shown activity against Gleevec-resistant patients bearing some point mutations but the “gate-keeper” mutations (e.g., T315I Bcr-Abl, T674I PDGFR?). Therefore, development of more novel small molecule tyrosine kinase inhibitors is still needed. The investigations of my group discovered several compounds which are effective against Gleevec-resistant tumor cells regardless of resistance to Gleevec. Dr. Pan and his collegues synthesized compounds including novel small molecule compounds of GZD824 and S116836, and discovered the effect of the third-generation of tyrosine kinase inhibitors (e.g. ponatinib, DCC-2036) on Gleevec-resistant T674I PDGFR? and D816V KIT. The compounds kill cells harboring gate-keeper mutantants of tyrosine kinases by lowering the expression of the oncoproteins (Bcr-Abl, KIT and PDGFRα). Examples include triptolide, pristimerin and SNS-032 (transcription inhibitors), homoharringtonine (a translation inhibitor), and celastrol (an hsp90 inhibitor).Cancer stem cells are believed to confer drug-resistance and relapse. Niclosamide is an oral antihelminthic drug for treating most tapeworm infection for about 50 years, and is also used as a molluscicide for water treatment in schistosomiasis control programs. Dr. Pan’s group first reported that niclosamide has a potent inhibitory activity against acute myelogenous leukemia (AML) cells. Of note, their findings pointed out that niclosamide effectively kills stem cells from patients with acute myelogenous leukemia but spared those from normal bone marrow. Ongoing projects are involved in develop more novel agents against cancer stem cells including ocular melanoma stem cells.
- Selected recent publications
1. Shen Y, Ren X, Ding K, Zhang Z, Wang D, Pan J. Antitumor activity of S116836, a novel tyrosine kinase inhibitor, against imatinib-resistant FIP1L1-PDGFRα-expressing cells. Oncotarget. 2014, in press. (IF 6.63).2. Jin B, Ding K, Pan J. Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing β-catenin signaling. Mol Cancer Ther. 2014. 2014; 13(5):1217-30 PMID:24552773. (IF 5.599).3. Jin Y, Ding K, Li H, Xue M, Shi X, Wang C, Pan J. Ponatinib efficiently kills imatinib-resistant chronic eosinophilic leukemia cells harboring gatekeeper mutant T674I FIP1L1-PDGFR?: roles of Mcl-1 and ?-catenin. Mol Cancer. 2014; 13(1):17. PMID: 24472312. (IF 5.134).4. Wu Y, Chen C, Sun X, Shi X, Jin B, Ding K, Yeung SC, Pan J. Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and Bcr-Abl oncogene addiction in malignant hematologic cells. Clin Cancer Res. 2012; 18(7):1966-1978. PMID: 22447844. (IF 7.837).5. Shi X, Zhang Y, Zheng J, Pan J. Reactive oxygen species in cancer stem cells. Antioxid Redox Signal. 2012. 16(11): 1215-1228. PMID: 22316005. (IF 7.189).6. Hong J, Hu K, Yuan Y, Sang Y, Bu Q, Chen G, Yang L, Li B, Huang P, Chen D, Liang Y, Zhang R, Pan J, Zeng YX, Kang T. CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma. J Clin Invest. 2012; 122(6):2165-75. PMID: 22585575. (IF 12.812).7. Jin Y, Lu Z, Ding K, Li J, Du X, Chen C, Sun X, Wu Y, Zhou J, Pan J. Antineoplastic mechanisms of niclosamide in acute myelogenous leukemia stem cells: inactivation of the NF-?B pathway and generation of reactive oxygen species. Cancer Res. 2010; 70(6): 2516–27. PMID: 20215516. (IF 8.65).8. Lu Z, Jin Y, Chen C, Li J, Cao Q, Pan J. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-?B signaling and depleting Bcr-Abl. Mol Cancer. 2010; 9(1):112. PMID: 20482842. (IF 5.134).9. Jin Y, Lu Z, Cao K, Zhu Y, Chen Q, Zhu F, Qian C, Pan J. The antitumor activity of homoharringtonine against human mast cells harboring the KIT D816V mutation. Mol Cancer Ther. 2010; 9(1):211-23. PMID: 20053766. (IF 5.599).10. Xu F, Shi X, Li S, Cui J, Lu Z, Jin Y, Lin Y, Pang J and Pan J. Design, synthesis, and biological evaluation of novel water-soluble triptolide derivatives: antineoplastic activity against imatinib-resistant CML cells bearing T315I mutant Bcr-Abl. Bioorg Med Chem. 2010; 18:1806–1815. PMID: 20149665. (IF 2.903).11. Shi X, Jin Y, Cheng C, Zhang H, Zou W, Zheng Q, Lu Z, Chen Q, Lai Y, Pan J. Triptolide inhibits Bcr-Abl transcription and induces apoptosis in STI571-resistant chronic myelogenous leukemia cells harboring T315I mutation. Clin Cancer Res. 2009; 15(5):1686-1697. PMID: 19240172. (IF 7.837).12. Pan J, Song E, Cheng C, Lee MH, Yeung SCJ. Farnesyltransferase inhibitors-induced autophagy: alternative mechanisms? Autophagy 2009; 5(1):129-31. PMID: 19066466. (IF 12.042).13. Pan J, Quintás-Cardama A, Kantarjian HM, Akin C, Manshouri T, Lamb P, Cortes JE, Tefferi A, Giles F, Verstovsek S. EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation. Blood. 2007; 109(1):315-22. PMID: 16912224. (IF 9.06).14. Pan J, Quintás-Cardama A, Kantarjian HM, Lamb P, Cortes JE, Giles FJ, Verstovsek S. The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-alpha-expressing cells through caspase-3-mediated cleavage of Mcl-1. Leukemia. 2007; 21(7):1395-404. PMID: 17495975. (IF 10.164).15. Pan J, She M, Xu Z, Sun L, and Yeung SCJ. Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res. 2005; 65:3671-3681. PMID: 15867362. (IF 8.65).16. Pan J and Yeung SC. Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors. Cancer Res. 2005; 65:9109-12. PMID: 16230362. (IF 8.65).