京都大学医生物学研究所 がん・幹細胞シグナル分野・准教授服部 鮎奈Ayuna HattoriDivision of Cell Fate Dynamics and Therapeutics Department of Biosystems ScienceInstitute for Life and Medical Sciences (LiMe), Kyoto University AbstractOne of the major factors influencing patient prognosis in cancer is malignancy progression, which tends to increase as the disease advances. In general, early-stage cancers are highly sensitive to chemotherapy and radiation; however, as the disease progresses, cancer cells frequently acquire treatment resistance and metastasize to multiple organs, leading to poor prognosis. As demonstrated by the success of various molecular targeted therapies, elucidating the mechanisms underlying cancer progression and developing therapies that target these mechanisms hold great promise for improving clinical outcomes. In our recent work, we discovered that the dynamics of the nucleolus undergo significant changes during disease progression in myeloid leukemia. Furthermore, we demonstrated that functional inhibition of key regulators involved in the organization of this nuclear compartment exerts marked therapeutic effects, even in advanced stages of leukemia. These findings were supported by studies using both in vivo mouse models and human leukemia cells. Alterations in nucleolar structure are known to correlate with cellular malignancy and stemness, not only in hematologic malignancies but also in embryonic stem cells. Although nucleolar function is suggested to be relevant across various cancer types, the molecular mechanisms involved remain largely unclear. Based on this background, the objective of our current research project is to identify and evaluate small-molecule compounds that inhibit nucleolar function by establishing a novel image-based analytical platform. Through this approach, we aim to develop innovative therapeutic strategies for treatment-resistant myeloid leukemia.はじめにがん予後に大きな影響を与える要因のひとつは，治療抵抗性や再発につながるがん進展・悪性化の有無である．従って，がんの進行を制御する機構を明らかにし，それを阻害あるいは反転させる治療― 68 ―新規 AI 画像解析法を活用した進行がん治療薬の開発Development…of…therapeutic…agents…for…advanced…cancerusing…a…novel…AI-based…image…analysis…method
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