Elucidation of molecular mechanisms of cancer progression by mechanical unloading

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22719
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: HIASA Masahiro 徳島大学, 大学院医歯薬学研究部(歯学域), 講師 (90511337)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 免荷 / 破骨細胞

Outline of Final Research Achievements

Breast cancer, lung cancer, and multiple myeloma are intractable diseases that frequently develop bone metastasis and osteolytic lesions. Osteolytic lesions of these cancers can cause bone pain, nerve damage, and fractures, which can leave patients bedridden. Furthermore, immobility due to bedridden status causes disuse muscle atrophy, bone atrophy, and increased susceptibility to infection, all of which contribute to cancer progression and poor prognosis. Therefore, it is desired for therapeutic strategies to prevent bedridden patients from directly leading to the progression of cancer. This study elucidated that the mechanism by which immobilization accelerates the progression of bone metastatic cancer involves the activation of osteoclasts, and demonstrated the efficacy of TAK-Pim signaling inhibitors as therapeutic agents targeting for this mechanism.

Free Research Field

矯正歯科

Academic Significance and Societal Importance of the Research Achievements

本研究は不動（寝たきり）による免荷で生じる骨髄微小環境の変化が、破骨細胞依存的にがん細胞の形質を転換させ、骨転移がんの進展を加速化するメカニズムを解明した。さらに、本研究で開発したTAK-Pimシグナル阻害薬は抗腫瘍作用を有する上に骨形成誘導作用を併せ持ち、転移をも克服することができ難治性のがん治療に光明をもたらす可能性がある。