Relationship between PI3K-Akt pathway activation and recurrence of early glottic cancer
| Project/Area Number |
19K18731
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | MACC1 / recurrence / glottic cancer / サイトカイン / がん遺伝子 / 早期声門癌 / 再発 / 頭頸部癌 |
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| Outline of Research at the Start |
Metastasis-associated with colon cancer 1は、PI3K/AKTシグナル経路を介してさまざまな悪性腫瘍の病態に関与している。しかし、頭頸部癌とMetastasis-associated with colon cancer 1の関連については報告がない。本研究では、頭頸部癌患者を対象に、PI3K/AKTシグナル経路に関する因子の網羅的な解析を行うとともに、検出された因子と治療効果などの臨床因子との関連を検討する。また、頭頸部癌モデルマウスを用いて、AKTの関連因子の発現を調べる。以上により、頭頸部癌に対する新規治療法やバイオマーカーの確立を目指す。
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| Outline of Final Research Achievements |
The transcriptional target of MACC1 is c-Met, the gene that encodes HGF. MACC1 is involved in the signal transduction of PI3K-Akt pathways. Moreover, the involvement of MACC1 in the inactivation of apoptosis-inducing factors and in cell cycle promotion in malignancies is thought to contribute to cancer infiltration and metastasis. MACC1 has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. However, a relationship between MACC1 and head and neck cancer has not been previously reported.
Johan et al. reported that the radioresistance of head and neck cancers is linked to PI3K-Akt pathway activation. As the PI3K-Akt pathway is assumed to be activated in MACC1-positive patients, we believe that MACC1 expression increase the risk of radioresistance. In the present study, we confirmed that MACC1 expression, in early stage glottic cancers, makes patients significantly more likely to experience recurrence after RT.
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| Academic Significance and Societal Importance of the Research Achievements |
早期声門癌においてMACC1が陽性であれば、RT、CRT後に有意に再発を来たしやすいことを確認した。MACC1陽性例は放射線抵抗性が高かったことが再発を来しやすい一因ではないかと考えられた。本検討において再発症例はRT単独症例のみでCRT症例では認められなかった。これは化学療法を追加したことで、放射線治療抵抗性があるものの治療強度が上がり根治し得た可能性が考えられた。
MACC1陽性の声門癌ではより放射線抵抗性が強いことが推察されるため、治療強度を上げたCRTを行うことで再発を防げる可能性も考えられ、今後のさらなる検討が必要と考えられた。
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Report
(5 results)
Research Products
(22 results)
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[Journal Article] Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma2022
Author(s)
Maki Akamatsu,Takuma Makino,Shinya Morita,Yohei Noda,Shin Kariya,Tomoo Onoda,Mizuo Ando,Yoshihiro Kimata,Kazunori Nishizaki,Mitsuhiro Okano,Aiko Oka,Kengo Kanai,Yoshihiro Watanabe,Yorihisa Imanishi
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Journal Title
Front Oncol
Volume: 12
Pages: 1010252-1010252
DOI
Related Report
Peer Reviewed / Open Access
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