Relationship between PI3K-Akt pathway activation and recurrence of early glottic cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18731
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Okayama University
• Principal Investigator: Makino Takuma 岡山大学, 大学病院, 助教 (50648706)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: MACC1 / recurrence / glottic cancer

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.

Free Research Field

耳鼻咽喉科

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。