Association between focal adhesion kinase and tumor immune responses for surgically treated hypopharyngeal carcinoma

• Project/Area Number: 18K09339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Omura Go 東京大学, 医学部附属病院, 届出研究員 (00601139)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 頭頸部原発粘膜悪性黒色腫 / 癌遺伝子 / NRAS / AYA世代舌癌 / 頭頸部粘膜悪性黒色腫 / 全ゲノム解析 / 頭頸部アルミノックス治療 / BCOR-CCNB3肉腫 / 遺伝子解析 / 遺伝子変異 / 次世代シーケンサー / 下咽頭癌 / focal adhesion kinase / PD-1 / 腫瘍免疫応答

Outline of Final Research Achievements

We focused on malignant melanoma, which has been reported to be associated with FAK, and used FFPE specimens from patients with primary mucosal malignant melanoma of the head and neck who were treated at the National Cancer Center Hospital. Mutational analysis of hotspot mutations of oncogenes as potential therapeutic targets was conducted using FFPE specimens from patients with primary mucosal malignant melanoma of the head and neck treated at the National Cancer Center Hospital. BRAFV600 mutations, which are found in nearly half of primary cutaneous malignant melanomas, were found in 0 cases, and NRAS and KIT mutations were found in 22 and 9% of cases, respectively. We also examined the prognosis of patients with AYA-onset tongue squamous cell carcinoma (TSCC) and those with TSCC that developed in other age groups using data from the Head and Neck registry of Japan, and reported that the AYA patients had a better prognosis.

Academic Significance and Societal Importance of the Research Achievements

術後補助療法あるいは再発転 移皮膚原発悪性黒色腫に対するBRAF阻害剤+MEK1/2阻害剤であるダブラフェニブ+トラメチニブでの薬物療法は頭頸部原発粘膜悪性黒色腫に用いられる可能性は非常に低いことがわかった。またNRASやKITの変異をターゲットとする治療が免疫チェックポイント阻害剤治療とは別に治療標的となる可能性があると考えている。AYA世代発症舌癌の予後については特に社会面、心理面で負担を及ぼすAYA世代患者に対して正しい知見を発することにより不安を軽減させることができると考えられる。

Research Products

• [Journal Article] Comparison of survival outcomes between adolescent and young adults and older adults with tongue squamous cell carcinoma: a nationwide database study using the Head and Neck Cancer Registry of Japan. (2023)
  • Author(s): Omura G, Yoshimoto S, Rikitake R, Eguchi K, Nakamizo M, Nibu K.
  • Journal Title: Int J Clin Oncol Volume: 28 Issue: 2 Pages: 221-228
  • DOI: 10.1007/s10147-022-02279-6
  • Peer Reviewed
• [Journal Article] Transnasal photoimmunotherapy with cetuximab sarotalocan sodium: outcomes on the local recurrence of nasopharyngeal squamous cell carcinoma. (2022)
  • Author(s): Omura G, Honma Y, Matsumoto Y, Shinozaki T, Itoyama M, Eguchi K, Sakai T, Yokoyama K, WatanabeT, Ohara A, Kato K, and Yoshimoto S
  • Journal Title: Auris Nusus Larynx Volume: in press Issue: 4 Pages: 641-645
  • DOI: 10.1016/j.anl.2022.06.004
  • Peer Reviewed
• [Journal Article] BCOR-CCNB3 sarcoma arising in the pharynx. (2022)
  • Author(s): Eguchi K, Omura G, Shimoi T, Kageyama D, Igaki H, Abe Y, Watanabe T, Aihara Y, Sakai A, Matsumoto Y, Sakai T, Yonemori K, Mori T, Yoshida A, and Yoshimoto S
  • Journal Title: Auris Nusus Larynx Volume: in press Issue: 4 Pages: 618-622
  • DOI: 10.1016/j.anl.2022.04.012
  • Peer Reviewed
• [Journal Article] Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade (2022)
  • Author(s): Sakai Toshihiko、Saito Yuki、Tateishi Yoko、Yamazawa Sho、Fukuoka Osamu、Kobayashi Kenya、Omura Go、Akashi Ken、Yoshida Masafumi、Ando Mizuo、Ebihara Yasuhiro、Yamasoba Tatsuya
  • Journal Title: International Journal of Clinical Oncology Volume: 27 Issue: 12 Pages: 1818-1827
  • DOI: 10.1007/s10147-022-02249-y
  • Peer Reviewed
• [Journal Article] Postoperative complications and swallowing function after jejunal and skin flap reconstruction for hypopharyngeal carcinoma- A multicenter retrospective study. (2022)
  • Author(s): Postoperative complications and swallowing function after jejunal and skin flap reconstruction for hypopharyngeal carcinoma- A multicenter retrospective study. Tokashiki K, Okamoto I, Okada T, Sato H, Yamashita T, Matsuki T, Kondo T, Fushimi C, Masubuchi T, Miura K, Omura G, and Tsukahara K.
  • Journal Title: J Clin Med Volume: 11 Issue: 5 Pages: 1464-1464
  • DOI: 10.3390/jcm11051464
  • Peer Reviewed
• [Journal Article] Uniform infection screening allowed safe head and neck surgery during the coronavirus disease 2019 pandemic in Japan (2021)
  • Author(s): Akiko I, Kobayashi K, Shiotsuka M, Sato T, Omura G, Matsumoto Y, Ikeda A, Sakai A, Eguchi K, Takano T, Matsumot F, Kobayashi O, Iwata S, Yoshimoto S.
  • Journal Title: Jpn J Clin Oncol . Volume: 51 Issue: 3 Pages: 400-407
  • DOI: 10.1093/jjco/hyaa195
  • Peer Reviewed / Open Access
• [Journal Article] Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases; 2 cm in Patients With Head and Neck Squamous Cell Carcinoma (2021)
  • Author(s): Tairo Kashihara, Satoshi Nakamura, Naoya Murakami, Kimiteru Ito, Yoshifumi Matsumoto, Kenya Kobayashi, Go Omura, Taisuke Mori, Yoshitaka Honma, Yuko Kubo, Hiroyuki Okamoto, Kana Takahashi, Koji Inaba, Kae Okuma, Hiroshi Igaki, Yuko Nakayama, Ken Kato, Fumihiko Matsumoto, Seiichi Yoshimoto and Jun Itami
  • Journal Title: Frontiers in oncology Volume: 11 Pages: 651409-651409
  • DOI: 10.3389/fonc.2021.651409
  • Peer Reviewed / Open Access
• [Journal Article] Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma (2021)
  • Author(s): Shigemasa Takamizawa, Yoshitaka Honma, Naoya Murakami, Taisuke Mori, Hiroki Oka, Shun Yamamoto, Tairo Kashihara, Kimiteru Ito, Yuko Kubo, Atsuo Ikeda, Fumihiko Matsumoto, Go Omura, Kenya Kobayashi, Jun Itami, Ken Kato, Seiichi Yoshimoto
  • Journal Title: Investigational New Drugs volume Volume: 39 Issue: 2 Pages: 560-570
  • DOI: 10.1007/s10637-020-00999-y
  • Peer Reviewed
• [Journal Article] Hybrid Intracavitary-Interstitial brachytherapy in a case of nasal vestibule cancer penetrating the hard palate (2021)
  • Author(s): Naoya Murakami, Go Omura, Wakako Yatsuoka, Hiroyuki Okamoto, Seiichi Yoshimoto, Takao Ueno and Jun Itami
  • Journal Title: BJR case reports Volume: 7 Issue: 4 Pages: 20200178-20200178
  • DOI: 10.1259/bjrcr.20200178
  • Peer Reviewed
• [Journal Article] Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence. (2020)
  • Author(s): Kobayashi K, Yoshimoto S, Ando M, Matsumoto F, Murakami N, Omura G, Honma Y, Matsumoto Y, Ikeda A, Sakai A, Eguchi K, Ito A, Eigitsu R, Yatabe Y, Mori T.
  • Journal Title: Oral oncology Volume: 113 Pages: 105091-105091
  • DOI: 10.1016/j.oraloncology.2020.105091
  • Peer Reviewed / Open Access
• [Journal Article] Pull-through resection without free-flap reconstruction for lateral wall oropharyngeal cancer. (2020)
  • Author(s): Matsumoto F, Kobayashi K, Omura G, Matsumura S, Matsumoto Y, Fukasawa M, Yoshimoto S.
  • Journal Title: Jpn J Clin Oncol. Volume: 50 Issue: 9 Pages: 1018-1022
  • DOI: 10.1093/jjco/hyaa079
  • Peer Reviewed
• [Journal Article] Risk Factors for Delayed Surgical Recovery and Massive Bleeding in Skull Base Surgery. (2020)
  • Author(s): Kobayashi K, Matsumoto F, Miyakita Y, Arikawa M, Omura G, Matsumura S, Ikeda A, Sakai A, Eguchi K, Narita Y, Akazawa S, Miyamoto S, Yoshimoto S.
  • Journal Title: Biomed Hub. Volume: 5 Issue: 2 Pages: 87-100
  • DOI: 10.1159/000507750
  • Peer Reviewed
• [Journal Article] Cite Share Salvage Chemotherapy After Nivolumab for Recurrent or Metastatic Head and Neck Carcinoma. (2020)
  • Author(s): Fushimi C, Okamoto I, Matsuki T, Masubuchi T, Okada T, Sato H, Tsukahara K, Kondo T, Yamashita T, Hanyu K, Omura GO, Takahashi H, Tada Y, Miura K.
  • Journal Title: Anticancer Res Volume: 40 Issue: 9 Pages: 5277-5283
  • DOI: 10.21873/anticanres.14532
  • Peer Reviewed
• [Journal Article] Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. (2020)
  • Author(s): Matsuki T, Okamoto I, Fushimi C, Takahashi H, Okada T, Kondo T, Sato H, Ito T, Tokashiki K, Tsukahara K, Hanyu K, Masubuchi T, Tada Y, Miura K, Omura G, Sawabe M, Kawakita D, Yamashita T
  • Journal Title: Cancers Volume: 12 Issue: 11 Pages: 3427-3427
  • DOI: 10.3390/cancers12113427
  • Peer Reviewed / Open Access
• [Journal Article] Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients. (2020)
  • Author(s): Matsuki T, Okamoto I, Fushimi C, Sawabe M, Kawakita D, Sato H, Tsukahara K, Kondo T, Okada T, Tada Y, Miura K, Omura G, Yamashita T
  • Journal Title: Cancer Med. Volume: 9 Issue: 14 Pages: 5015-5024
  • DOI: 10.1002/cam4.3124
  • Peer Reviewed / Open Access
• [Journal Article] Post-operative complications due to salvage total laryngectomy for recurrent laryngeal cancer after radiotherapy a multicentre retrospective study. (2020)
  • Author(s): Okamoto I, Matsuki T, Sato H, Kondo T, Fushimi C, Okada T, Miura K, Yamashita T, Omura G, and Tsukahara K.
  • Journal Title: Acta Otolaryngol Volume: 140 Issue: 2 Pages: 170-174
  • DOI: 10.1080/00016489.2019.1699251
  • Peer Reviewed
• [Journal Article] A surgical approach to schwannomas originating from the esophageal branch of the recurrent laryngeal nerve: Pictorial essay. (2019)
  • Author(s): Kobayashi K, Matsumoto Y, Matsumoto F, Sato T, Mori T, Tsuchida T, Omura G, Matsumura S, Ikeda A, Sakai A, Eguchi K, and Yoshimoto S.
  • Journal Title: Head Neck Volume: 41 Issue: 11 Pages: 4054-4059
  • DOI: 10.1002/hed.25921
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of nivolumab in 100 patients with recurrent or metastatic head and neck cancer a retrospective multicenter study. (2019)
  • Author(s): Okamoto I, Sato H, Kondo T, Koyama N, Fushimi C, Okada T, Miura K, Matsuki T, Yamashita T, Omura G, and Tsukahara K.
  • Journal Title: Acta otolaryngol Volume: 139 Issue: 10 Pages: 918-925
  • DOI: 10.1080/00016489.2019.1648867
  • Peer Reviewed
• [Journal Article] Common carotid artery ligation at the proximal side before rupture in patients with ligation or occlusion of the external carotid artery at risk of carotid blowout syndrome. (2019)
  • Author(s): Matsumoto F, Matsumura S, Mori T, Mori A, Omura G, Matsumoto Y, Fukasawa M, Kobayashi K, Yoshimoto S.
  • Journal Title: Jpn J Clin Oncol Volume: 49 Issue: 9 Pages: 839-844
  • DOI: 10.1093/jjco/hyz075
  • Peer Reviewed / Open Access
• [Journal Article] All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma (2019)
  • Author(s): Kobayashi K, Yoshimoto S, Matsumoto F, Ando M, Murakami N, Omura G, Fukasawa M, Matsumoto Y, Matsumura M, Akamatsu M, Hiraoka N, Eigitsu R, and Mori T
  • Journal Title: Annals of Surgical Oncology Volume: 印刷中 Issue: 7 Pages: 2294-2303
  • DOI: 10.1245/s10434-019-07287-x
  • Peer Reviewed / Open Access
• [Journal Article] Association between aldehyde dehydrogenase-2 polymorphisms, alcohol consumption, and prognosis in Japanese patients with hypopharyngeal cancer (2018)
  • Author(s): 小村 豪, 安藤 瑞生, 小林 謙也, 福岡 修, 明石 健, 齊藤 祐毅, 吉田 昌史, 山岨 達也
  • Journal Title: Toukeibu Gan Volume: 44 Issue: 4 Pages: 365-369
  • DOI: 10.5981/jjhnc.44.365
  • NAID: 130007585329
  • ISSN: 1349-5747, 1881-8382
  • Peer Reviewed
• [Presentation] 頭頸部悪性腫瘍全国登録データベースを用いた本邦におけるAYA世代発症舌癌の臨床的検討 (2022)
  • Author(s): 小村 豪、力武 諒子、吉本 世一
  • Organizer: 第46回日本頭頸部癌学会
• [Presentation] 当院における頭頸部粘膜悪性黒色腫手術症例の臨床的検討 (2022)
  • Author(s): 小村 豪、松本 吉史、坂井 利彦、坂井 梓、江口 紘太郎、渡邉 嶺、相原 勇介、三輪 好、向井 昌功、林 崇明、吉本 世一
  • Organizer: 第32回日本頭頸部外科学会
• [Presentation] Surgical extent of parotid cancer: primary to neck (2022)
  • Author(s): Go Omura
  • Organizer: 14th International Facial Nerve Symposium
  • Int'l Joint Research / Invited
• [Presentation] 上咽頭癌化学放射線療法後の局所再発に対して頭頸部イルミノックス治療を施行した１例 (2022)
  • Author(s): 小村 豪、松本 吉史、伊東山 舞、江口 紘太郎、坂井 利彦、渡邉 嶺、相原 勇介、本間 義崇、吉本 世一
  • Organizer: 第31回日本頭頸部外科学会総会
• [Presentation] 頭頸部悪性腫瘍全国登録データベースを用いた本邦におけるAYA世代発症舌癌の臨床的検討 (2022)
  • Author(s): 小村 豪、力武 諒子、吉本 世一
  • Organizer: 第46回日本頭頸部癌学会総会
• [Presentation] 早期口腔癌に対するセンチネルリンパ節生検vs予防的頸部郭清術の術後頸部機能評価ならびに安全性について (2021)
  • Author(s): 小村 豪、吉本 世一、塚原 清彰、三浦 弘規、横山 純吉、平野 滋、上村 裕和、菅澤 正、本間 明宏、甲能 直幸、長谷川 泰久
  • Organizer: 第45回日本頭頸部癌学会総会
• [Presentation] 頭頸部粘膜悪性黒色腫症例におけるドライバー遺伝子の変異解析 (2019)
  • Author(s): 小村 豪、森 泰昌、松本 吉史、赤松 摩紀、坂井 梓、池田 篤生、松村 聡子、小林 謙也、松本 文彦、吉本 世一
  • Organizer: 第43回日本頭頸部癌学会
• [Presentation] 下咽頭喉頭癌手術例における病理学的転移リンパ節個数と遠隔再発に関する検討 (2018)
  • Author(s): 小村 豪、森 泰昌、松本 吉史、松村 聡子、深澤 雅彦、小林 謙也、松本 文彦、吉本 世一
  • Organizer: 日本頭頸部癌学会総会
• [Presentation] 頭頸部遊離組織移植手術症例における術後譫妄発症の危険因子についての検討 (2018)
  • Author(s): 小村 豪、小林 謙也、松村 聡子、坂井 梓、池田 篤生、松本 吉史、深澤 雅彦、松本 文彦、吉本 世一
  • Organizer: 日本頭頸部外科学会総会