今月の研究者

高野 利実

高野 利実

私は、1998年に東京大学を卒業し、当時はまだ診療科名としてはほとんど知られていなかった「腫瘍内科」を志し、東京大学医学部附属病院の内科と放射線科で研修しました(今でも放射線科医局員です)。2000年より東京共済病院呼吸器科で乳癌と肺癌の診療に携わり、2002年より国立がんセンター中央病院内科レジデントで腫瘍内科全般のトレーニングを受けました。国立がんセンターでは、主に肺内科に所属し、当時、肺癌に対して初めて承認された分子標的治療薬であるゲフィチニブ(イレッサ)の効果予測因子や肺毒性予測因子についての研究にも取り組みました。ゲフィチニブなどEGFRチロシンキナーゼ阻害薬(EGFR-TKI)の効果を規定するのはEGFR遺伝子変異であるという報告が米国から届いた(先を越された)衝撃は今でも忘れられませんが、EGFR遺伝子変異が日本人肺癌患者で多いという点を活かして、その後、各種の解析結果を報告することができました。EGFR-TKIの効果予測因子がEGFR遺伝子変異なのか、EGFR遺伝子コピー数なのか、という議論で世界が二分されたときに、「遺伝子変異派」の一員としてアカデミックな議論の中心に立てたのも、いい経験でした。この研究では、2005年に米国臨床腫瘍学会(ASCO)のMerit Awardと世界肺癌会議(WCLC)のYoung Investigator Awardを受賞しました。
2005年に東京共済病院に戻り、念願の「腫瘍内科」を開設しましたが、医員は1人だけで、患者さんが増える中、燃え尽き症候群のような状態になりかけました。やはり仲間が必要だと感じ、2008年、帝京大学医学部附属病院腫瘍内科開設に伴い講師として赴任しました。縦割り構造の強い大学病院で臓器横断的な診療科を展開することの難しさもありましたが、仲間と助け合いながら、臨床研究に携わり、若い人を教育することの喜びを感じることができました。
そして、2010年、虎の門病院臨床腫瘍科に最年少部長として赴任し、私にとっては3ヶ所目となる「腫瘍内科」を立ち上げました。これまでの経験を活かして、「日本一の腫瘍内科をつくる」ことを目標に掲げ、日本の一般病院における腫瘍内科のモデルとなるべく、診療、研究、教育の3面においてこれまでになかったような取り組みを展開しています。診療面では、関連する診療科と連携しながら、悪性腫瘍一般の薬物療法と緩和ケアに取り組み、患者数や外来化学療法件数も着実に増加しています。研究面では、全国規模の臨床試験グループで中心的に活動し、数多くの臨床試験や医師主導治験を主導しているほか、企業治験件数も確実に増加しています。また、分子標的治療薬や免疫チェックポイント阻害薬の効果や副作用を予測するバイオマーカーを探索するトランスレーショナルリサーチにも積極的に取り組んでいます。教育面では、「本物の腫瘍内科医」として世界を舞台に活躍する人材を育成するために、レジデント教育に力を入れています。
2010年に医師3名でスタートした臨床腫瘍科ですが、2019年度には、医師12名(部長1名、医長1名、医員3名、フェロー1名、レジデント6名)と臨床研究コーディネーター等の事務職員6名の計18名に増えました。志をともにする仲間に支えられていることに感謝しながら、さらなる高みを目指したいと考えています。

私には3つの目標があります。
①日本に本物の腫瘍内科を広めること
②世界をリードする臨床研究を行うこと
③「Human-Based Medicine(HBM)」を実践すること
です。
①としては、虎の門病院に日本一の腫瘍内科をつくって、本物の腫瘍内科医を育成しつつ、全国的には、日本臨床腫瘍学会などの活動を通じて、日本における腫瘍内科の普及と発展を目指しています。
②として、私は、西日本がん研究機構(WJOG)乳腺委員会委員長として、全国規模の臨床試験や医師主導治験を手掛けており、世界規模の臨床試験グループと協調・競争しながら、世界を変えるようなエビデンスを発信していきたいと考えています。
③のHBMは、私が一番大事にしているものです。本物の腫瘍内科をつくり、世界をリードする臨床研究を展開するその先にあるべきものは、「患者さんの幸せ」です。日々の診療でも、目指すのは、「一人ひとりの患者さんの、その人なりの幸せ」です。そんな医療のことを、HBMと呼んでいます。
著書「がんとともに、自分らしく生きる―希望をもって、がんと向き合う『HBM』のすすめ―」(2016年、きずな出版)では、これまでにお会いした患者さんとのエピソードを紹介しつつ、がんとの向き合い方やHBMの考え方などについて、書き綴っています。

発表・論文

発表・論文

1 Akamatsu H, Harada H, Tokunaga S, Yoshimura N, Ikeda H, Oizumi S, Sugimoto N, Takano T, Murakami H, Nishimura Y, Yamamoto N, Nakagawa K: A phase II study of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations (WJOG6911L). Clinical Lung Cancer 20:e25-e27, 2019

2 Yokoe T, Hayashida T, Nagayama A, Seki T, Takahashi M, Takano T, Abe T, Kitagawa Y: Effectiveness of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis. The Oncologist Published Online October 17, 2018

3 Oka S, Inoshita N, Miura Y, Oki R, Miyama Y, Nagamoto S, Ogawa K, Sakaguchi K, Kondoh C, Kurosawa K, Urakami S, Takano T, Okaneya T. Prognostic value of BAP1 expression in clear cell renal cell carcinoma with inferior vena cava tumor thrombosis. Urol Oncol. 36:365.e9-365.e14, 2018

4 Yamashiro H, Sawaki M, Masuda N, Okumura Y, Takano T, Tokunaga E, Saito T, Sagara Y, Yamazaki K, Kawaguchi Y, Lee T, Ozaki S, Yamagami K, Yamamoto N, Kuroi K, Suwa H, Ohtani S, Ito T, Yasuno S, Morita S, Ohno S, and Toi M: Survival outcomes of retreatment with trastuzumab and cytotoxic chemotherapy for HER2-positive recurrent patients with breast cancer who had been treated with neo/adjuvant trastuzumab plus multidrug chemotherapy: a Japanese multicenter observational study. Breast Cancer (Auckl), 12:1-7, 2018

5 Kuwayama T, Nakamura S, Hayashi N, Takano T, Tsugawa K, Sato T, Kitani A, Okuyama H, and Yamauchi H: Randomized multicenter phase II trial of neoadjuvant therapy comparing weekly nab-paclitaxel followed by FEC with docetaxel followed by FEC in HER2- early-stage breast cancer. Clin Breast Cancer 18:474-480, 2018

6 Yamamoto Y, Iwata H, Ueno T, Taira N, Kashiwaba M, Takahashi M, Tada H, Tsugawa K, Toyama T, Niikura N, Hara F, Fujisawa T, Yoshinami T, Saji S, Takano T, Masuda N, Morita S, Toi M, and Ohno S: A randomized, open-label, Phase III trial of pertuzumab retreatment in HER2-positive locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab and chemotherapy: the Japan Breast Cancer Research Group-M05 PRECIOUS study. Jpn J Clin Oncol 48:855–859, 2018

7 Takano T, Tsurutani J, Takahashi M, Yamanaka T, Sakai K, Ito Y, Fukuoka J, Kimura H, Kawabata H, Tamura K, Matsumoto K, Aogi K, Sato K, Nishio K, Nakagawa K, Saeki T: A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP. The Breast 40:67-75, 2018

8 Ozaki Y, Shindoh J, Gonoi W, Nishioka Y, Kondoh C, Tanabe Y, Matoba S, Kuroyanagi H, Hashimoto M, Takano T: Changes in CT morphology can be an independent response marker for patients receiving regorafenib for colorectal liver metastases: Retrospective pilot study. BMC Cancer18:138, 2018

9 Masuda N, Toi M, Yamamoto N, Iwata H, Kuroi K, Bando H, Ohtani S, Takano T, Inoue K, Yanagita Y, Kasai H, Morita S, Sakurai T, Ohno S: Efficacy and safety of trastuzumab, lapatinib, and paclitaxel neoadjuvant treatment with or without prolonged exposure to anti-HER2 therapy, and with or without hormone therapy for HER2-positive primary breast cancer: a randomised, five-arm, multicentre, open-label phase II trial. Breast Cancer 25:407-415, 2018

10 Kawaguchi H, Masuda N, Nakayama T, Aogi K, Anan K, Ito Y, Ohtani S, Sato N, Saji S, Takano T, Tokunaga E, Nakamura S, Hasegawa Y, Hattori M, Fujisawa T, Morita S, Yamaguchi M, Yamashita H, Yamashita T, Yamamoto Y, Yotsumoto D, Toi M, Ohno S: Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study. Current Medical Research and Opinion 34, 49–54, 2018

11 Miura Y, Sukawa Y, Hironaka S, Mori M, Nishikawa K, Tokunaga S, Okuda H, Sakamoto T, Taku K, Nishikawa K, Moriwaki T, Negoro Y, Kimura Y, Uchino K, Shinozaki K., Shinozaki H, Musha N, Yoshiyama H, Tsuda T, Miyata Y, Sugimoto N, Shirakawa T, Ito M, Yonesaka K, Yoshimura K, Boku N, Nosho K, Takano T, Hyodo I: Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G). Gastric Cancer 21, 84–95, 2018

12 Ozaki Y, Tanabe Y, Tamura N, Ogura T, Kondoh C, Miura Y, Yoshimura K, Kawabata H, Takano T: Impact on disease-free survival of the duration of ovarian function suppression, as postoperative adjuvant therapy, in premenopausal women with hormone receptor-positive breast cancer: a retrospective single-institution study. Breast Cancer 25:343-349, 2018

13 Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, Oudard S, Retz MM, Castellano D, Bamias A, Fléchon A, Gravis G, Hussain S, Takano T, Leng N, Kadel EE, Banchereau R, Hegde PS, Mariathasan S, Cui N, Shen X, Derleth CL, Green MC, Ravaud A: Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 391:748-757, 2018

14 Motoshima T, Miura Y, Wakigami N, Kusada N, Takano T, Inoshita N, Okaneya T, Sugiyama Y, Kamba T, Takeya M, Komohara Y: Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma. Medical Molecular Morphology. 51:57-63, 2018

15 Bang YJ, Takano T, Lin CC, Fasanmade A, Yang H, Danaee H, Asato T, Kalebic T, Wang H, and Doi T: TAK-264 (MLN0264) in previously treated Asian patients with advanced gastrointestinal carcinoma expressing guanylyl cyclase C: results from an open-label, non-randomized phase 1 study. Cancer Res Treat 50: 398-404, 2018

16 Sasaki T, Kato Y, Sato A, Usui N, Baba E, Takano T, Susumu N, Ohnishi K, Nishimoto H, Kiura K: A questionnaire survey of pharmacists regarding the clinical practice guidelines for the appropriate use of granulocyte-colony stimulating factors. J Pharm Health Care Sci 4:2, 2018

17 Anzai H, Nozawa H, Tanaka J, Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Ushiku T, Ishihara S, Takano T, Fukayama M, Watanabe T: Giant leiomyosarcoma of the rectum with lymph node metastasis: A case report and review of the literature. International Journal of Surgery Case Reports 34:27-31, 2017

18 Tomizawa K, Miura Y, Fukui Y, Hanaoka Y, Toda S, Moriyama J, Inoshita N, Ozaki Y, Takano T, Matoba S, and Kuroyanagi H: Curative resection for locally advanced sigmoid colon cancer using neoadjuvant chemotherapy with FOLFOX plus panitumumab. Int J Surg Case Rep 31:128-131, 2017

19 Watanabe J, Ito Y, Saeki T, Masuda N, Takano T, Takao S, Nakagami K, Tsugawa K, Nakagawa S, Kanatani K, and Nakayama T: Safety evaluation of trastuzumab emtansine in Japanese patients with HER2-positive advanced breast cancer. In vivo 31:493-500, 2017

20 Miura Y, Inoshita N, Ikeda M, Oki R, Ozaki Y, Tanabe Y, Kuosawa K, Urakami S, Kono T, Okaneya T, and Takano T: Loss of BAP1 protein expression in metastatic sites of the first recurrence to predict prognosis in patients with clear cell renal cell carcinoma. Urologic Oncology 35:386–391, 2017

21 Tanabe Y, Shimizu C, Hamada A, Hashimoto K, Ikeda K, Nishizawa D, Hasegawa J, Shimomura A, Ozaki Y, Tamura N, Yamamoto H, Yunokawa M, Yonemori K, Takano T, Kawabata H, Tamura K, Fujiwara Y: Paclitaxel‑induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese. Cancer Chemother Pharmacol 79:1179–1186, 2017

22 Koganemaru S, Inoshita N, Miura Y, Miyama Y, Fukui Y, Ozaki Y, Tomizawa K, Hanaoka Y, Toda S, Suyama K, Tanabe Y, Moriyama J, Fujii T, Matoba S, Kuroyanagi H, Takano T: Prognostic value of programmed death-ligand 1 expression in patients with stage III colorectal cancer. Cancer Science 108:853-858 2017

23 Ozaki Y, Shindoh J, Miura Y, Nakajima H, Oki R, Uchiyama M, Masuda J, Kinowaki K, Kondoh C, Tanabe Y, Tanaka T, Haruta S, Ueno M, Kitano S, Fujii T, Udagawa H, Takano T: Serial pseudoprogression of metastatic malignant melanoma in a patient treated with nivolumab: A case report. BMC Cancer 17:778. 2017

24 Ishizuka N, Takano T, Miura Y, Suyama K, Shimomura A, and Matsushima E: Psychological distress and Resilience among partners of cancer patients receiving outpatient chemotherapy. International Journal of Clinical Medicine, 8:481-495, 2017

25 Shitara K, Yonesaka K, Denda T, Yamazaki K, Moriwaki T, Tsuda M, Takano T, Okuda H, Nishina T, Sakai K, Nishio K, Tokunaga S, Yamanaka T, Boku N, Hyodo I, Muro K: Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. Cancer Science 107:1843-1850, 2016

26 Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, and Ohashi Y: Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 17:90-98, 2016

27 Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, and Kang YK: Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol 26:2097-2101, 2015

28 Yamashiro H, Iwata H, Masuda N, Yamamoto N, Nishimura R, Ohtani S, Sato N, Takahashi M, Kamio T, Yamazaki K, Saito T, Kato M, Lee T, Ohno S, Kuroi K, Takano T, Takada M, Yasuno S, Morita S, and Toi M: Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients. Int J Clin Oncol 20:709-22, 2015

29 Body JJ, Bone HG, de Boer RH, Stopeck A, Van Poznak C, Damião R, Fizazi K, Henry DH, Ibrahim T, Lipton A, Saad F, Shore N, Takano T, Shaywitz AJ, Wang H, Bracco OL, Braun A, and Kostenuik PJ: Hypocalcaemia in patients with metastatic bone disease treated with denosumab. Eur J Cancer 51:1812–1821, 2015

30 Ozaki Y, Miura Y, Koganemaru S, Suyama K, Inoshita N, Fujii T, Hashimoto M, Tamura T, Takeuchi K, Takano T: Ewing sarcoma of the liver with multilocular cystic mass formation: a case report. BMC Cancer 15:16, 2015

31 Kosaka Y, Rai Y, Masuda N, Takano T, Saeki T, Nakamura S, Shimazaki R, Ito Y, Tokuda Y, Tamura K: Phase III placebo-controlled double-blind randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer. 23:1137-43, 2015

32 Ozaki Y, Miura Y, and Takano T: Resistance to androgen-pathway drugs in prostate cancer. N Engl J Med 371:2233-2234, 2014

33 Miura Y, Imamura CK, Fukunaga K, Katsuyama Y, Suyama K, Okaneya T, Mushiroda T, Ando Y, Takano T, and Tanigawara Y: Sunitinib-induced severe toxicities in a Japanese patient with the ABCG2 421 AA genotype. BMC Cancer 14:964, 2014

34 Masuda N, Higaki K, Takano T, Matsunami N, Morimoto T, Ohtani S, Mizutani M, Miyamoto T, Kuroi K, Ohno S, Morita S and Toi M: A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer Cancer Chemother Pharmacol 74:229-38, 2014

35 Tomizawa K, Suyama K, Matoba S, Hanaoka Y, Toda S, Moriyama J, Shimomura A, Miura Y, Kumada H, Kuroyanagi H, Takano T: The safety of chemotherapy for colorectal cancer patients with hepatitis C virus infection. Med Oncol 31:212, 2014.

36 Soma S, Tsuta K, Takano T, Hatanaka Y, Yoshida A, Suzuki K, Asamura H, and Tsuda H: Intratumoral distribution of EGFR-amplified and EGFR-mutated cells in pulmonary adenocarcinoma. Pathol Res Pract 210:155-160, 2014

37 Tanioka M, Sasaki M, Shimomura A, Fujishima M, Doi M, Matsuura K, Sakuma T, Yoshimura K, Saeki T, Ohara M, Tsurutani J, Takano T, Kawabata H, Mukai H, Naito Y, Hirokaga K, Takao S, and Minami H: Pathologic complete response after neoadjuvant chemotherapy in human epidermal growth factor receptor 2-overexpressing breast cancer according to hormonal receptor status. The Breast 23:466-472, 2014

38 Hanaoka M, Kawabata H, Iwatani T, Takano T, and Miura D: Reduction of toxicity by reversing the order of infusion of docetaxel and cyclophosphamide. Reduction of toxicity by reversing the order of infusion of docetaxel and cyclophosphamide. Chemotherapy. 59:93-98, 2013

39 Miura Y, Suyama K, and Takano T: Treatment of acute promyelocytic leukemia. N Engl J Med 369:1471-1472, 2013

40 Sagara Y, Sato K, Fukuma E, Higaki K, Mizutani M, Osaki A, Takano T, Tokuda Y, Ohno S, Masuda N, Suzuki M, and Saeki T: The efficacy and safety of FSK0808, filgrastim biosimilar: a multicenter, non-randomized study in Japanese patients with breast cancer. Jpn J Clin Oncol 43:865–873, 2013

41 Miura Y, Theriault RL, Naito Y, Suyama K, Shimomura A, Iwatani T, Miura D, Kawabata H, Kumada H, and Takano T: The safety of chemotherapy for breast cancer patients with hepatitis C virus infection. J Cancer 4:519-523, 2013

42 Miura Y, Suyama K, Shimomura A, Miyakawa J, Kobayashi H, Uki A, Okaneya T, and Takano T: Radiation-induced esophagitis exacerbated by everolimus. Case Rep Oncol 6:320-324, 2013

43 Shitara K, Yuki S, Yamazaki K, Naito Y, Fukushima H, Komatsu Y, Yasui H, Takano T, and Muro K: Validation study of a prognostic classification in patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy. J Cancer Res Clin Oncol. 139:595-603, 2013

44 Kaji D, Miura Y, and Takano T: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 367:179-180, 2012

45 Akiyama S, Suyama K, and Takano T: Colorectal-Cancer Screening. N Engl J Med 366:2129-2131, 2012

46 Stopeck AT, Lipton A, Martín M, Body J-J, Paterson A, Steger GG, Tonkin K, de Boer RH, Fujiwara Y, Yardley D, Jassem J, Takano T, Solal-Celigny P, Fan M, and Braun A: Results from the 2-year open-label extension treatment phase of a pivotal phase 3 study of denosumab in patients with breast cancer and bone metastases previously treated with zoledronic acid or denosumab. European Journal of Cancer Volume 48, Supplement 4, April 2012, Pages S3

47 Kaji D, Miura Y, and Takano T: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 366:663-666, 2012

48 Hanaoka M, Takano T, and Kawabata H: Exemestane for breast-cancer prevention N Engl J Med 365:1056-1058, 2011

49 Shigeta K, Naito Y, and Takano T: Early prostate cancer — treat or watch? N Engl J Med 365:568-569, 2011

50 Shigeta K, Miura Y, Naito Y, and Takano T: Cabazitaxel for castration-resistant prostate cancer. Lancet 377:121, 2011

51 Naito Y, Miura Y, Takano T: Neoadjuvant chemotherapy or primary surgery in advanced ovarian cancer. N Engl J Med 363:2370-2372, 2010

52 Takano T: Treatment of Lung Cancer. N Engl J Med 361:2485-2487, 2009

53 Jida M, Toyooka S, Mitsudomi T, Takano T, et al: Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment. Cancer Sci 100:1931-1934, 2009

54 Takano T, Ota S, Hori A, Seki N, and Eguchi K: Can Epidermal Growth Factor Receptor–Fluorescent in Situ Hybridization Predict Clinical Benefit From Cetuximab Treatment in Patients With Non–Small-Cell Lung Cancer? J Clin Oncol 27:464-465, 2009

55 Takano T, Fukui T, Ohe Y, et al: EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: a historical comparison of patients treated before and after gefitinib approval in Japan. J Clin Oncol 26: 5589-5595, 2008

56 Fukui T, Ohe Y, Tsuta K, Furuta K, Sakamoto H, Takano T, et al: Prospective study of the accuracy of EGFR mutational analysis by high-resolution melting analysis in small samples obtained from patients with non–small cell lung cancer. Clin Cancer Res 14:4751-4757, 2008

57 Toyooka S, Takano T, Kosaka T, et al: Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. Cancer Science 99:303-308, 2008

58 Takano T, Ohe Y, Tsuta K, et al: Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non–small cell lung cancer treated with gefitinib. Clin Cancer Res 13:5385-5390, 2007

59 Okano T, Kondo T, Fujii K, Nishimura T, Takano T, Ohe Y, Tsuta K, Matsuno Y, Gemma A, Kato H, Kudoh S, and Hirohashi S: Proteomic signature corresponding to the response to gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma. Clin Cancer Res 13:799-805, 2007

60 Nomoto K, Tsuta K, Takano T, et al: Detection of EGFR mutations in archived cytologic specimens of non-small cell lung cancer using high-resolution melting analysis. Am J Clin Pathol 126:608-615, 2006

61 Takano T, Ohe Y, Sekine I, Kunitoh H, Yoshida T, and Tamura T: In Reply. J Clin Oncol 24:1221, 2006

62 Takano T and Ohe Y: Erlotinib in lung cancer. N Engl J Med 353:1739-1741, 2005

63 Takano T, Ohe Y, Sakamoto H, et al: Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23:6829-6837, 2005

64 Takano T, Ohe Y, Kusumoto M et al.: Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib. Lung Cancer 45: 93-104, 2004

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