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• Ryohei Katayama, Ph.D.

Ryohei Katayama, Ph.D.

Affiliation

Education & Professional Career

Area of Research

molecular targeting therapy of cancer / drug resistance / cellular signaling in cancer / cancer stem (initiating) cells / apoptosis signaling / circadian rhythms and cancer

Membership

・Japanese Cancer Association (2003-)
・Japanese Association for Molecular Targeted Therapy of Cancer (2006-)
・American Association for Cancer Research (2009-)
・Japan Society of Medical Oncology (2013-)
・Japan Lung Cancer Society (2016-)

Awards

  4/2005　 AACR Scholar-in Training Award
  4/2012　 AACR Scholar-in Training Award
10/2015　 JCA prize for encouragement
 6/2017　  Incitement Award of the JAMTTC

Research Projects

One of the goal of our research is to identify the molecular mechanisms of the drug resistance against molecular targeted therapy in cancer, and find the therapeutic strategies to overcome the resistance. Especially, we are focusing on lung cancer. Lung cancer is the leading cause of cancer death in Japan. According to the development of sequencing technologies and the enormous effort of the research, lung cancer is now defined by driver oncogene mutations, such as EGFR or KRAS active mutation, ALK, ROS1, or RET gene rearrangement, and molecular target therapy to each oncogenic mutated (altered) protein such as EGFR or ALK are used in clinic. For example, for the treatment of ALK rearranged lung cancer, currently ALK tyrosine kinase inhibitors, crizotinib, alectinib or ceritinib (only in US and EU) are used in clinic based on the remarkable responses in clinical trials. Although the molecular targeting drugs often shows drastic responses, tumor inevitably relapses due to the acquired resistance. To understand the resistance mechanisms to molecular targeted drugs, mainly tyrosine kinase inhibitors, in ALK, ROS1, RET rearranged NSCLC, we are establishing the resistant cells in vitro and in vivo and examine the mechanisms of resistance. In addition, by collaborating with the physician in our cancer institute hospital, we also examined the resistant mechanisms using the samples derived from molecular targeting drug refractory patients under approved IRB with signed Informed consent.
Another goal of our research is to unveil the characteristics of “cancer stem cells” and identify the molecular target of cancer stem cells. When the anti-cancer drugs (either chemotherapy or molecular targeting drug) effectively worked, most of the cancer cell were killed. However, tumor often relapses because some cells were left behind. Those persistent / resistant cells are thought to be cancer stem (-like) cells (CSCs). CSCs are reported to have higher tumorigenicity and share some properties with normal stem cells, such as a resistance to drugs and toxins, multi-potency to re-population. To understand the characteristics of CSCs and identify novel therapeutic targets in CSCs, we establish patient derived xenograft model using the surgical specimens of colorectal cancer under approved IRB with signed Informed consent.

Publications

1.Ono F, Chiba S, Isaka Y, Matsumoto S, Ma B, Katayama R, Araki M, Okuno Y. Improvement in predicting drug sensitivity changes associated with protein mutations using a molecular dynamics based alchemical mutation method. Sci Rep. 2020 Feb 7;10(1):2161.

2.Arai S, Takeuchi S, Fukuda K, Taniguchi H, Nishiyama A, Tanimoto A, Satouchi M, Yamashita K, Ohtsubo K, Nanjo S, Kumagai T, Katayama R, Nishio M, Zheng MM, Wu YL, Nishihara H, Yamamoto T, Nakada M, Yano S. Osimertinib Overcomes Alectinib Resistance Caused by Amphiregulin in a Leptomeningeal Carcinomatosis Model of ALK-Rearranged Lung Cancer. J Thorac Oncol. 2020 Jan 21. pii: S1556-0864(20)30022-8.

3.Yanagitani N, Uchibori K, Koike S, Tsukahara M, Kitazono S, Yoshizawa T, Horiike A, Ohyanagi F, Tambo Y, Nishikawa S, Fujita N, *Katayama R, *Nishio M. Drug resistance mechanisms in Japanese anaplastic lymphoma kinase-positive non-small cell lung cancer and the clinical responses based on the resistant mechanisms. Cancer Sci. 2020 Mar;111(3):932-939.

4.Takahashi K, Seto Y, Okada K, Uematsu S, Uchibori K, Tsukahara M, Oh-Hara T, Fujita N, Yanagitani N, Nishio M, Okubo K, *Katayama R. Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non-small cell lung cancer. Thorac Cancer. 2020 Mar;11(3):581-587.

5.*Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, Kamai Y, Tominaga Y, Takeda Y, Kagoshima Y, Shimizu Y, Seto Y, Oh-hara T, Koike S, Nakao N, Hanzawa H, Watanabe K, Yoda S, Yanagitani N, Hata A, Shaw AT, Nishio M, Fujita N, Isoyama T. The new-generation selective ROS1/NTRK Inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nature Commun. 2019; Aug 9;10(1):3604.

6.Gong B., Kiyotani K., Sakata S., Nagano S., Kumehara S., Baba S., Besse B., Yanagitani N., Friboulet L., Nishio M., Takeuchi K., Kawamoto H., Fujita N., *Katayama R. Secreted PD-L1 variants mediate resistance to PD-L1 blockade therapy in non-small cell lung cancer. J Exp Med. 2019;216(4):982-1000.

7.Fukuda K, Takeuchi S, Arai S, Katayama R, Nanjo S, Tanimoto A, Nishiyama A, Nakagawa T, Taniguchi H, Suzuki T, Yamada T, Nishihara H, Ninomiya H, Ishikawa Y, Baba S, Takeuchi K, Horiike A, Yanagitani N, Nishio M, Yano S. Epithelial-to-mesenchymal transition is a mechanism of ALK inhibitor resistance in lung cancer independent of ALK mutation status. Cancer Res. 2019; 79:1658-1670.

8.Okada K, Araki M, Sakashita T, Ma B., Kanada R, Yanagitani N, Horiike A, Koike S, Oh-Hara T, Watanabe K, Tamai K, Maemondo M, Nishio M, Ishikawa T, Okuno Y, Fujita N, *Katayama R Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance. EBioMedicine, 2019; 41:105-119.

9.Ukaji T, Takemoto A, Katayama R, Takeuchi K, and Fujita N. A safety study of newly generated anti-podoplanin-neutralizing antibody in cynomolgus monkey (Macaca fascicularis). Oncotarget, 2018: 9, 33322-33336.

10.Sakamoto K, Katayama R, Asaka R, Sakata S, Baba S, Nakasone H, Koike S,Tsuyama N, Dobashi A, Sasaki M, Ichinohasama R, Takakuwa E, Yamazaki R, Takizawa J, Maeda T, Narita M, Izutsu K, Kanda Y, Ohshima K, Takeuchi K. Recurrent 8q24rearrangement in blastic plasmacytoid dendritic cell neoplasm: association withimmunoblastoid cytomorphology, MYC expression, and drug response. Leukemia. 2018; 32(12):2590-2603.

11.Gong B, Oh-Hara T, Fujita N, *Katayama R. 3D culture system containing gellan gum restores oncogene dependence in ROS1 rearrangements non-small cell lung cancer. Biochem Biophys Res Commun. 2018 Jun 22;501(2):527-533.

12.Uchibori K, Inase N, Nishio M, Fujita N, *Katayama R. Identification of Mutation Accumulation as Resistance Mechanism Emerging in First-Line Osimertinib Treatment. J Thorac Oncol. 2018 Jul;13(7):915-925.

13.Ariyasu R, Nishikawa S, Uchibori K, Oh-Hara T, Yoshizawa T, Dotsu Y, Koyama J, Saiki M, Sonoda T, Kitazono S, Yanagitani N, Horiike A, Inase N, Kasahara K, Nishio M, *Katayama R. High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer. Lung Cancer. 2018 Mar;117:1-6.

14.Ohashi Y, Okamura M, Katayama R, Fang S, Tsutsui S, Akatsuka A, Shan M, Choi HW, Fujita N, Yoshimatsu K, Shiina I, Yamori T, Dan S. Targeting the Golgi apparatus to overcome acquired resistance of non-small cell lung cancer cells to EGFR tyrosine kinase inhibitors. Oncotarget. 2017 Dec 6;9(2):1641-1655.

15.*Katayama R. Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer. Cancer Sci. 2018 Mar;109(3):572-580. Review.

16.Fuse MJ, Okada K, Oh-hara T, Ogura H, Fujita N, *Katayama R. Mechanisms of resistance to NTRK inhibitors and therapeutic strategies in NTRK1-rearranged cancers. Mol Cancer Ther. 2017, October 1;16 (10):2130-2143.

17.Ogura H, Nagatake-Kobayashi Y. Adachi J, Tomonaga T, Fujita N, *Katayama R. TKI-addicted ROS1-rearranged cells are destined to survival or death by the intensity of ROS1 kinase activity. Sci Rep. 2017, July 17; 7: 5519

18.Tanaka N, Mashima T, Mizutani A, Sato A, Aoyama A, Gong B, Yoshida H, Muramatsu Y, Nakata K, Matsuura M, Katayama R, Nagayama S, Fujita N, Sugimoto Y, *Seimiya H. APC Mutations as a Potential Biomarker for Sensitivity to Tankyrase Inhibitors in Colorectal Cancer. Mol Cancer Ther. 2017, 16(4):752-762.

19.Uchibori K, Inase N, Araki M, Kamada M, Sato S, Okuno Y, Fujita N, *Katayama R. Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nature Commun., 2017 Mar 13;8:14768.

20.*Katayama R. Therapeutic strategies and mechanisms of drug resistance in anaplastic lymphoma kinase (ALK)-rearranged lung cancer. Pharmacol Ther. 2017 Sep;177:1-8. Review.

21.Gainor JF, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R, Dagogo-Jack I, Gadgeel S, Schultz K, Singh M, Chin E, Parks M, Lee D, DiCecca RH, Lockerman E, Huynh T, Logan J, Ritterhouse LL, Le LP, Muniappan A, Digumarthy S, Channick C, Keyes C, Getz G, Dias-Santagata D, Heist RS, Lennerz J, Sequist LV, Benes CH, Iafrate AJ, Mino-Kenudson M, Engelman JA, *Shaw AT. Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Discov. 2016, 6(10):1118-1133.

22.Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, *Engelman JA. Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med. 2016 Jan 7;374(1):54-61.

23.*Katayama R, Sakashita T, Yanagitani N, Ninomiya H, Horiike A, Friboulet L, Gainor JF, Motoi N, Dobashi A, Sakata S, Tambo Y, Kitazono S, Sato S, Koike S, John Iafrate A, Mino-Kenudson M, Ishikawa Y, Shaw AT, Engelman JA, Takeuchi K, *Nishio M, *Fujita N. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer. EBioMedicine, 2016 Jan; 3: 54–66.

24.Zou HY, Friboulet L, Kodack DP, Engstrom LD, Li Q, West M, Tang RW, Wang H, Tsaparikos K, Wang J, Timofeevski S, Katayama R, Dinh DM, Lam H, Lam JL, Yamazaki S, Hu W, Patel B, Bezwada D, Frias RL, Lifshits E, Mahmood S, Gainor JF, Affolter T, Lappin PB, Gukasyan H, Lee N, Deng S, Jain RK, Johnson TW, Shaw AT, Fantin VR, *Smeal T. PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell, 2015 Jul 13;28(1):70-81.

25.*Katayama R, Lovly CM, Shaw AT. Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm for precision cancer medicine. Clin Cancer Res. 2015 May 15;21(10):2227-35. Review.

26.Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S,Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, *Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nature Commun. 2015 Mar 11;6:6377.

27.Katayama R, Kobayashi Y, Friboulet L, Lockerman EL, Koike S, Shaw AT, Engelman JA, *Fujita N. Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer. Clin Cancer Res. 2015 Jan 1;21(1):166-74.

28.Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, Frias RL, Gainor JF, Amzallag A, Greninger P, Lee D, Kalsy A, Gomez-Caraballo M, Elamine L, Howe E, Hur W, Lifshits E, Robinson HE, Katayama R, Faber AC, Awad MM, Ramaswamy S, Mino-Kenudson M, Iafrate AJ, Benes CH, *Engelman JA., Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science, 2014 Dec 19;346(6216):1480-6.

29.Aoyama A†, Katayama R†, Oh-Hara T, Sato S, Okuno Y, *Fujita N. Tivantinib (ARQ 197) exhibits antitumor activity by directly interacting with tubulin and overcomes ABC transporter-mediated drug resistance. Mol Cancer Ther. 2014 Dec;13(12):2978-90. †: co-first authors

30.Katayama R, Friboulet L, Koike S, Lockerman EL, Khan TM, Gainor JF, Iafrate AJ, Takeuchi K, Taiji M, Okuno Y, Fujita N, *Engelman JA, *Shaw AT. Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96.

31.Friboulet L†, Li N†, Katayama R†, Lee CC, Gainor JF, Crystal AS, Michellys PY, Awad MM, Yanagitani N, Kim S, Pferdekamper AC, Li J, Kasibhatla S, Sun F, Sun X, Hua S, McNamara P, Mahmood S, Lockerman EL, Fujita N, Nishio M, Harris JL, Shaw AT, *Engelman JA. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-73. †: co-first authors

32.Gainor JF, Varghese AM, Ou SH, Kabraji S, Awad MM, Katayama R, Pawlak A, Mino-Kenudson M, Yeap BY, Riely GJ, Iafrate AJ, Arcila ME, Ladanyi M, Engelman JA, Dias-Santagata D, *Shaw AT. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013 Aug 1;19(15):4273-81.

33.Awad MM, Katayama R, McTigue M, Liu W, Deng YL, Brooun A, Friboulet L, Huang D, Falk MD, Timofeevski S, Wilner KD, Lockerman EL, Khan TM, Mahmood S, Gainor JF, Digumarthy SR, Stone JR, Mino-Kenudson M, Christensen JG, Iafrate AJ, Engelman JA, *Shaw AT. Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395-401.

34.Katayama R, Aoyama A, Yamori T, Qi J, Oh-hara T, Song Y, Engelman JA, *Fujita N. Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition. Cancer Res. 2013 May 15;73(10):3087-96.

35.Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, Drew L, Saeh JC, Crosby K, Sequist LV, Iafrate AJ, *Engelman JA. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17.

36.Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, Massion PP, Siwak-Tapp C, Gonzalez A, Fang R, Mark EJ, Batten JM, Chen H, Wilner KD, Kwak EL, Clark JW, Carbone DP, Ji H, Engelman JA, Mino-Kenudson M, Pao W, *Iafrate AJ. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012 Mar 10;30(8):863-70.

37.Katayama R, Khan TM, Benes C, Lifshits E, Ebi H, Rivera VM, Shakespeare WC, Iafrate AJ, Engelman JA, *Shaw AT. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40.

38.Morishita D, Takami M, Yoshikawa S, Katayama R, Sato S, Kukimoto-Niino M, Umehara T, Shirouzu M, Sekimizu K, Yokoyama S, *Fujita N. Cell-permeable carboxyl-terminal p27(Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase. J Biol Chem. 2011 Jan 28;286(4):2681-8.

39.Ehata S, Johansson E, Katayama R, Koike S, Watanabe A, Hoshino Y, Katsuno Y, Komuro A, Koinuma D, Kano MR, Yashiro M, Hirakawa K, Aburatani H, Fujita N, *Miyazono K. Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. Oncogene. 2011 Apr 7;30(14):1693-705.

40.Sequist LV, Gettinger S, Senzer NN, Martins RG, Jänne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, Sweeney J, Walker JR, Fritz C, Ross RW, Grayzel D, Engelman JA, Borger DR, Paez G, *Natale R. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010 Nov 20;28(33):4953-60.

41.Misawa A, Katayama R, Koike S, Tomida A, Watanabe T, *Fujita N. AP-1-Dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells. Oncol Res., 2010;19(1):23-33.

42.Katayama R, Ishioka T, Takada S, Takada R, Fujita N, Tsuruo T, and *Naito M. Modulation of Wnt signaling by the nuclear localization of cellular FLIP-L., J Cell Sci.,1;123(Pt 1):23-8., 2010

43.Katayama R, Koike S, Sato S, Sugimoto Y, Tsuruo T, and *Fujita N. Dofequidar fumarate sensitizes cancer stem–like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP-mediated drug export. Cancer Sci., 100:2060-2068, 2009.

44.Morishita D, Katayama R, Sekimizu K, Tsuruo T and *Fujita N. Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels., Cancer Res., 68:5076–5085, 2008

45.Kurata A, Katayama R, Watanabe T, Tsuruo T and *Fujita N. TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling., Cancer Sci., 99:1827-1834, 2008

46.Tokuda E, *Fujita N, Oh-hara T, Sato S, Kurata A, Katayama R, Itoh T, Takenawa T, Miyazono K, Tsuruo T. Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology domain-interacting protein, down-regulates PI3K/Akt signaling and suppresses tumor growth in vivo., Cancer Res., 67:9666-9676, 2007

47.Ishioka T, Katayama R, Kikuchi R, Nishimoto M, Takada S, Takada R, Matsuzawa S, Reed JC, Tsuruo T and *Naito M. Impairment of the ubiquitin-proteasome system by cellular FLIP., Genes Cells, 12: 735-744, 2007

48.Noguchi T, Miyachi H, Katayama R, Naito M and *Hashimoto Y. Cell differentiation inducers derived from thalidomide. Bioorg Med Chem Lett., 15: 3212-3215, 2005

49.Naito M†, Katayama R†, Ishioka T, Suga A, Takubo K, Nanjo M, Hashimoto C, Taira M, Takada S, Takada R, Kitagawa M, Matsuzawa S, Reed JC and Tsuruo T. Cellular FLIP inhibits beta-catenin ubiquitylation and enhances Wnt signaling., Mol Cell Biol., 24: 8418-8427, 2004, †: co-first authors

50.Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T, Tsuruo T and *Naito M. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function., Nat Cell Biol., 6: 849-860, 2004

51.Tomita T, Katayama R, Takikawa R, *Iwatsubo T. Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments., FEBS Lett. 520:117-121, 2002

• JFCR
• The Cancer Institute Hospital of JFCR
• Cancer Institute
• Cancer Chemotherapy Center
• Cancer Precision Medicine Center
• NEXT-Ganken Program
• School of Cytotechnology

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