• Researcher Profile

    Kwok-Kin Wong, MD, PhD

     
    Scientific Director, Belfer Institute for Applied Cancer Science
    Physician


    Professor of Medicine, Harvard Medical School

    Center/Program

    Thoracic Oncology

    Office phone: 617-632-6084
    Fax: 617-582-7683
    Website: Wong Lab Website

    Preferred contact method: office phone

    View Physician Profile
     
     

    Interests

    Lung cancer, Developmental therapeutics

    Area of Research

    Pathogenesis of Human Lung Cancer


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    D810B
    Boston, MA 02215

    Recent Awards

    • Team Science Award AACR, 2010
    • Tisch Family Outstanding Award in Translational Research, 2008
    • Sidney Kimmel Foundation Scholar, 2004
    • Tisch Foundation Solid Tumor Scholar Award, 2004

    Research

    Pathogenesis of Human Lung Cancer

     As a basic/translational physician scientist, I focus on advancing our understanding of the pathogenesis and genetic alterations involved in lung tumorigenesis and testing novel lung cancer therapeutics in vivo, with the goal of developing approaches to improve outcomes for lung cancer patients.  


    My lab has experience using novel approaches to advance our understanding of lung cancer pathogenesis and uncover potential treatment modalities. Major scientific achievements with important clinical implications have been focused in 3 areas: (1) discovering novel genetic alterations in human lung cancer that are important in lung cancer initiation, progression and acquired resistance to initially effective novel therapeutics, (2) generating and characterizing genetically engineered mouse models based on novel lung-relevant human genetic alterations to genetically validate the importance of these mutations and for preclinical testing of targeted therapeutics, and (3) pioneering the paradigm of using these mouse models in clinical trials in mice and humans in parallel, to guide future targeted human clinical trials.  


    My work using genetically engineered mouse lung cancer models to validate oncogenic drivers and test novel therapeutics against specific genetic oncogenic drivers has been acknowledged by the international cancer scientific community as a novel means for credentialing new genetic alterations, and has changed the way innovative therapeutics are tested preclinically. This new paradigm has changed cancer drug development and facilitated design of rationally and genetically stratified human cancer clinical trials. Several global pharmaceutical companies and academic centers have adopted the murine co-clinical trial paradigm for drug development.  


    The DFCI Belfer Center focus is on novel cancer target discovery/validation and novel drug development, with 50 personnel. As Director, I have integrated academic, industry and clinical resources/expertise to enhance success in scientifically informed oncology drug discovery. The Institute’s excellence in early-stage biology, with Belfer scientists who have industry experience collaborating with DFCI clinical and academic investigators, enables our scientists to define the best targets and delineate the optimal clinical path for targeted cancer therapies, with the potential for accelerating cancer care approaches.


    In summary, my laboratory, clinical care, mentorship, and Belfer Center leadership have enabled me to build an influential investigative and clinical approach, with major scientific discoveries that have been internationally recognized for the rapid development and application of novel strategies to research and management of lung and other cancers. I use this constellation of tools to make a meaningful impact on lung cancer outcomes.

    Select Publications

    • Wong KK, Maser RS, Bachoo R, Menon J, Carrasco D, Gu Y, Alt F, DePinho R. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 2003;421:643-8.
    • Kobayashi S, Ji H, Yuza Y, Meyerson M, Wong KK, Tenen DG, Halmos B. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res 2005;65:7096-101
    • Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, DePinho RA. High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A 2005;102:9625-30.
    • Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac L.R, Padera R, Bronson R. T, Kim W, Jänne P.A, Shapiro G.I, Tenen D, Johnson B.E, Weissleder R, Sharpless N.E, Wong K-K. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR targeted therapies. Cancer Cell. 2006 9(6): 485-95. Epub 2006 May 25.
    • Li D, Shimamura T, Ji H, Chen L, Haringsma HJ, McNamara K, Liang MC, Perera SA, Zaghlul S, Borgman CL, Kubo S, Takahashi M, Sun Y, Chirieac LR, Padera RF, Lindeman N, Jänne PA, Thomas RK., Meyerson ML, Eck MJ, Engelman JA, Shapiro GI, Wong K-K. Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell. 2007 Jul;12 (1):81-93.
    • Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera S, Liang MC, Cai D, Naumov GN, Bao L, Contreras C, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Christiani DC, Lin X, Shapiro GI, Jänne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong K-K. LKB1 modulates lung cancer differentiation and metastasis. Nature. 2007 Aug 16;448(7155):807-10.
    • Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, Chirieac LR, Kaur R, Lightbown A, Simendinger J, Li T, Padera RF, García-Echeverría C, Weissleder R, Mahmood U, Cantley LC, Wong K-K. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2008 Dec;14(12):1351-6. PMCID: PMC2683415
    • Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong K-K. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A., 2009 January 13; 106(2): 474–479. PMCID: PMC2626727
    • Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong K-K (co-senior), Eck MJ, Gray NS, Jänne PA. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24;462 (7276):1070-4. PMCID: PMC287958
    • Carretero J, Shimamura T, Rikova K, Jackson AL, Wilkerson MD, Borgman CL, Buttarazzi MS, Sanofsky BA, McNamara KL, Brandstetter KA, Walton ZE, Gu TL, Silva JC, Crosby K, Shapiro GI, Maira SM, Ji H, Castrillon DH, Kim CF, García-Echeverría C, Bardeesy N, Sharpless NE, Hayes ND, Kim WY, Engelman JA, Wong K-K. Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. Cancer Cell. 2010 Jun 15;17(6):547-59. PMCID: PMC2901842
    • Chen Z, Sasaki T, Tan X, Carretero J, Shimamura T, Li D, Xu C, Wang Y, Aldelmant GO, Capelletti M, Lee HJ, Rodig SJ, Borgman CL, Park SI, Kim HR, Padera RF Jr, Marto J, Gray N, Kung AL, Shapiro GI, Janne PA, Wong K-K. Inhibition of ALK, PI3K/MEK and HSP90 in Murine Lung Adenocarcinoma Induced by EML4-ALK Fusion Oncogene. Cancer Res. 2010 Dec 1;70(23):9827-36. Epub 2010 Oct 15. PMCID: PMC3043107
    • Chen Z, Cheng K, Walton Z, Wang Y, Ebi H, Shimamura T, Liu Y, Tupper T, Ouyang J, Li J, Gao P, Woo MS, Xu C, Yanagita M, Altabef A, Wang S, Lee C, Nakada Y, Peña CG, Sun Y, Franchetti Y, Yao C, Saur A, Cameron MD, Nishino M, Hayes DN, Wilkerson MD, Roberts PJ, Lee CB, Bardeesy N, Butaney M, Chirieac LR, Costa DB, Jackman D, Sharpless NE, Castrillon DH, Demetri GD, Jänne PA, Pandolfi PP, Cantley LC, Kung AL, Engelman JA, Wong K-K. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature. 2012 Mar 18. doi: 10.1038/nature10937. PMCID: 3385933
    • Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong K-K, Engelman JA. Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models. Cancer Cell. 2013 Jan 14;23(1):121-8. Epub 2012 Dec 13. PMCID: PMC3667614
    • Chen Z, Akbay EA, Mikse OR, Tupper T, Cheng K, Wang Y, Tan X, Altabef A, Woo SA, Chen L, Reibel J, Janne PA, Engelman JA, Sharpless NE, Kung AL, Shapiro GI, Wong K-K. Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance. Clin Cancer Res. 2013 Dec 10. PMCID: PMC3947539
    • Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong K-K Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013 Sep 27. DOI: 10.1158/2159-8290.CD-13-0310 PMCID: PMC3864135.
    • Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, Reibel JB, Walton Z, Ji H, Watanabe H, Jänne PA, Castrillon DH, Rustgi AK, Bass AJ, Freeman GJ, Padera RF, Dranoff G, Hammerman PS, Kim CF, Wong K-K. Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression. Cancer Cell. 2014 May 12;25(5):590-604. doi: 10.1016/j.ccr.2014.03.033. Epub 2014 May 1. PMCID: PMC4112370
    • Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T, Zhang H, Palakurthi S, Jang J, Lelais G, DiDonato M, Bursulaya B, Michellys PY, Epple R, Marsilje TH, McNeill M, Lu W, Harris J, Bender S, Wong K-K, Jänne PA, Eck MJ. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 May 25;534(7605):129-32. doi: 10.1038/nature17960.
    • Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, Buczkowski KA, Liu Y, Awad MM, Denning WL, Diao L, Wang J, Parra Cuentas ER, Wistuba II, Soucheray M, Thai TC, Asahina H, Kitajima S, Altabef A, Cavanaugh JD, Rhee K, Gao P, Zhang H, Fecci PE, Shimamura T, Hellmann M, Heymach JV, Hodi FS, Freeman GJ, Barbie DA, Dranoff G, Hammerman PS, Wong K-K. STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T cell activity in the lung tumor microenvironment. Cancer Res. 2016 Feb 1. pii: canres.1439.2015. DOI: 10.1158/0008-5472.CAN-15-1439. PMCID: PMC4775354
    • Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong K-K, Hammerman PS. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016 Feb 17;7:10501. doi: 10.1038/ncomms10501.

    Trainees

    • Hongbin, Ji, PhD
    • Perera, Samanthi, PhD
    • Shimamura, Takeshi, PhD
    • Liang, Chen, PhD
    • Liang, Mei-Chih (Amy), PhD
    • Tan, Xiao Hong (Joy), PhD
    • Gandhi, Leena, MD, PhD
    • Carretero, Julian, PhD
    • Xu, Chunxiao, PhD
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