片山量平

所属

経歴

和歌山県生まれ
2001年 3月　東京大学薬学部 卒業
2005年 4月　日本学術振興会 特別研究員（DC2）
2006年 3月　東京大学大学院薬学系研究科 博士課程修了 薬学博士
2006年 4月　（財）癌研究会 癌化学療法センター 基礎研究部 研究員
2010年 3月　日本学術振興会 海外特別研究員（常勤研究者）にて米国留学
　　　　　　（留学先；Harvard Medical School/ MGH Cancer Center)
2012年 7月  （公財）がん研究会 がん化学療法センター 基礎研究部 研究員（復職）
2015年10月　(公財）がん研究会 がん化学療法センター 基礎研究部　主任研究員
2017年10月 （公財）がん研究会 がん化学療法センター 基礎研究部　部長

研究分野

・腫瘍生物学（がん分子標的治療・がん免疫療法と耐性）
・分子細胞生物学

 

所属学会・研究会

・日本癌学会
・アメリカ癌学会
・日本がん分子標的治療学会
・日本臨床腫瘍学会
・日本肺癌学会
・日本分子生物学会

受賞

2005年4月　 AACR Scholar-in Training Award
2012年4月　 AACR Scholar-in Training Award
2015年6月　 日本がん分子標的治療学会　優秀演題賞
2015年10月  日本癌学会　奨励賞
2017年6月　 日本がん分子標的治療学会　研究奨励賞
2018年2月　 BMS Award in Nagoya Symposium 2018
2018年4月　 科学技術分野の文部科学大臣表彰 若手科学者賞
2019年9月　 日本癌学会　JCA-Mauvernay Award

研究テーマ

がん分子標的療法とがん免疫療法に対する耐性機構の研究

肺がんはがんの中で最も死亡者が多く，より効果的な治療法の開発が切望されています。進行肺がんでは，外科手術による治療が困難な場合が多く，薬物療法や放射線療法が中心となっています。薬物療法としては近年までは細胞障害性の抗がん剤による化学療法が中心でしたが、この約10年の間にEGFRチロシンキナーゼ阻害薬（GefitinibやErlotinibなど）の登場と、EGFR活性化型変異の発見を契機に，分子標的薬の有用性が高まってきております。さらに2007年には、 強力ながん遺伝子としてALK融合遺伝子が発見され、現在ではALKチロシンキナーゼ阻害薬が5剤承認され使用されております。近年になり、 RET，ROS1，NTRKと様々な融合遺伝子陽性肺がんが見つかっており、これらに対しては各種分子標的薬の臨床試験が行われており、すでに複数のがん分子標的治療薬が承認されています。
EGFR変異やALK融合遺伝子のように標的となる遺伝子異常がある症例では対応する分子標的治療薬が顕著な腫瘍縮小効果を示すことが多いものの、治療を始めてから半年〜数年程度するとほとんどのケースにおいて治療抵抗性を獲得した耐性腫瘍が出現することが大きな問題となっており、耐性の分子機構解明と耐性克服法の発見が、より効果的な薬物療法の発展にとって重要です。そこで我々は、（１）培養細胞を用いて分子標的薬耐性細胞を作成し、その耐性機構について検討すること、（２）マウスに腫瘍細胞を移植したXenograftモデルを用いて、耐性腫瘍の作製および耐性機構の検索、耐性克服薬の効果について検討し、（３）実際に分子標的薬での治療を受けた患者様由来の検体（耐性前後の検体）を用いて耐性機構を検索する、などの方法を駆使し研究を進めています。
また、近年様々ながん種において重要な治療法の1つとなってきたがん免疫療法についても、獲得耐性の出現が問題となってきています。我々は、がん免疫療法、特に免疫チェックポイントっ阻害薬に対する獲得耐性機構についても、マウスモデルと患者臨床検体を用いて研究を進めております。

 

原著論文　(*: corresponding author)

1.Takemoto A, Takagi S, Ukaji T, Gyobu N, Kakino M, Takami M, Kobayashi A, Lebel M, Kawaguchi T, Sugawara M, Tsuji-Takayama K, Ichihara K, Funauchi Y, Ae K, Matsumoto S, Sugiura Y, Takeuchi K, Noda T, Katayama R, and Fujita N, Targeting podoplanin for the treatment of osteosarcoma. Clin Can Res. in press

2.Ito K, Nagata K, *Ohta S, Matsuda Y, Ukai T, Yasuda I, Ota A, Kobayashi R, Mio Kabata M, Sankoda N, Maeda T, Woltjen K, Yang L, Maruyama R, Katayama R,Yamamoto T, *Yamada Y, The oncogene-dependent resistance to reprogramming unveils cancer therapeutic targets. Cell Reports.in press

3.Shimizu Y, Okada K, Adachi J, Abe Y, Narumi R, Uchibori K, Yanagitani N, Koike S, Takagi S, Nishio M, Fujita N, *Katayama R. GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer. npj Precis Onc. 6: 16 (2022)

4.Tanimura K, *Yamada T, Okada K, Nakai K, Horinaka M, Katayama Y, Morimoto K, Ogura Y, Takeda T, Shiotsu S, Ichikawa K, Watanabe S, Morimoto Y, Iwasaku M, Kaneko Y, Uchino J, Taniguchi H, Yoneda K, Matoba S, Sakai T, Uehara H, Yano S, Kusaba T, Katayama R, and Takayama K, HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features. npj Precis Onc. 6: 5 (2022)

5.Sagawa R, Sakata S, Gong B, Seto Y, Takemoto A, Takagi S, Ninomiya H, Yanagitani N, Nakao M, Mun M, Uchibori K, Nishio M, Miyazaki Y, Shiraishi Y, Ogawa S, Kataoka K, Fujita N, Takeuchi K, *Katayama R. Soluble PD-L1 through alternative polyadenylation works as a decoy in lung cancer immunotherapy. JCI insight. 7(1):e153323, 2022.

6.Takagi S, Sasaki Y, Koike S, Takemoto A, Seto Y, Haraguchi M, Ukaji T, Kawaguchi T, Sugawara M, Saito M, Funauchi Y, Ae K, Matsumoto S, Fujita N, *Katayama R. Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis. Oncogene. 2021 Jul 23, 40:5548-5558, doi: 10.1038/s41388-021-01956-6.

7.Oguri, T., Sasada, S., Seki, S., Murata, S., Tsuchiya, Y., Ishioka, K., Takahashi, S., Seki, R., Hirose, S., Katayama, R., Nakamura, M. A case of hyperprogressive disease following atezolizumab therapy for pulmonary pleomorphic carcinoma with epidermal growth factor receptor mutation. Respir. Med. Case Rep. 33: 101405 (2021).

8.Tachiwana H, Dacher M, Maehara K, Harada A, Seto Y, Katayama R, Ohkawa Y, Kimura H, Kurumizaka H, Saitoh N. Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay. Elife. 2021 May 10;10:e66290.

9.Yoshizawa T, Uchibori K, Araki M, Matsumoto S, Ma B, Kanada R, Seto Y, Oh-hara T, Koike S, Ariyasu R, Kitazono S, Ninomiya H, Takeuchi K, Yanagitani N, Takagi S, Kishi, K, Fujita N, Okuno Y, Nishio M, *Katayama R. Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity. npj Precis Onc. April 16, 5, 32 (2021).

10.Ariyasu R, Uchibori K, Sasaki T, Tsukahara M, Kiyotani K, Yoshida R, Ono Y, Kitazono S, Ninomiya H, Ishikawa Y, Mizukami Y, Yanagitani N, Fujita N, Nishio M, *Katayama R. Monitoring EGFR C797S mutation in Japanese NSCLC patients with serial cell free DNA evaluation using digital droplet PCR. Cancer Sci. 2021 Jun;112(6):2371-2380.

11.Ukaji T, Takemoto A, Shibata H, Kakino M, Takagi S, Katayama R, Fujita N. Novel knock-in mouse model for the evaluation of the therapeutic efficacy and toxicity of human podoplanin-targeting agents. Cancer Sci. 2021 Jun;112(6):2299-2313.

12.Mizuta H, Okada K, Araki M, Adachi J, Takemoto A, Kutkowska J, Maruyama K, Yanagitani N, Oh-Hara T, Watanabe K, Tamai K, Friboulet L, Katayama K, Ma B, Sasakura Y, Sagae Y, Kukimoto-Niino M, Shirouzu M, Takagi S, Simizu S, Nishio M, Okuno Y, Fujita N, *Katayama R. Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer. Nature Commun. 2021 Feb 24;12(1):1261.

13.Furuta H, Araki M, Masago K, Sagae Y, Fujita S, Seto K, Shimizu J, Horio Y, Sasaki E, Hosoda W, Katayama R, Okuno Y, Hida T. Novel resistance mechanisms including L1196Q, P1094H, and R1248_D1249insertion in three patients with non-small-cell lung cancer following ALK tyrosine kinase inhibitor treatment. J Thorac Oncol. 2021 Mar;16(3):477-482.

14.Ariyasu R, Yanagitani N, Tadokoro K, Yamaguchi T, Uchibori K, Kitazono S, Fujita N, *Katayama R, *Nishio M. Efficacy of EGFR tyrosine kinase inhibitors in patients having EGFR-activating mutations with or without BIM polymorphisms. Cancer Chemother Pharmacol. 2020 Oct;86(4):517-525.

15.Papadopoulos KP, Borazanci E, Shaw AT, Katayama R, Shimizu Y, Zhu VW, Sun TY, Wakelee HA, Madison R, Schrock AB, Senaldi G, Nakao N, Hanzawa H, Masaya T, Isoyama T, Nakamaru K, Deng C, Li M, Fran F, Zhao Q, Gao Y, Seto T, Janne PA, Ou SI. US phase 1 first-in-human study of taletrectinib (DS-6051b/AB-106), a ROS1/TRK inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2020 Sep 15;26(18):4785-4794.

16.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.

17.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.

18.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.

19.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.

20.*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.

21.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.

22.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.

23.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.

24.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.

25.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.

26.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.

27.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.

28.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.

29.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.

30.*Katayama R. Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer. Cancer Sci. 2018 Mar;109(3):572-580.doi: 10.1111/cas.13504. Epub 2018 Feb 15. Review.

31.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.

32.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. Scientific Reports. 2017, July 17; 7: 5519

33.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.

34.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.

35.*Katayama R. Therapeutic strategies and mechanisms of drug resistance in anaplastic lymphoma kinase (ALK)-rearranged lung cancer. Pharmacol Ther.2017 Sep;177:1-8. doi: 10.1016/j.pharmthera.2017.02.015. Epub 2017 Feb 7. Review.,

36.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.

37.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.

38.*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.

39.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.

40.*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.

41.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.

42.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.

43.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.

44.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

45.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.

46.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

47.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.

48.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.

49.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.

50.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.

51.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.

52.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.

53.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.

54.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.

55.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.

56.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.

57.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

58..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.

59.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

60.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

61.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

62.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

63.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

64.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

65.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

66.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