大阪大学大学院医学系研究科癌創薬

Identification of novel small-molecule inhibitors targeting KDM5B and evaluation of their antitumour effects (Cancer Med, 2026)

Dr. Hara et al. identified a novel series of KDM5B inhibitors through structure-based optimization following screening of compounds targeting the histone demethylase KDM5B, a key epigenetic regulator implicated in cancer. Lead compounds exhibited potent KDM5B inhibition, low-micromolar antiproliferative activity across the cancer cell panel, and significant antitumour efficacy in xenograft models. Notably, we demonstrated enhanced tumour suppression and, when combined with RNA-based in vivo CAR-T cell therapy, induced chromatin accessibility changes in tumour and immune cell populations. These findings highlight a promising epigenetic therapeutic candidate that potentiates antitumour immunity through chromatin remodelling. Thus, discovery of a potent KDM5B inhibitor that rewires chromatin accessibility and augments antitumour responses, provides a new avenue for epigenetic cancer immunotherapy.

Targeting fibroblast activation protein in solid tumors via CAR-mRNA delivery promotes durable regression in solid tumor models (Scientific Reports, 2025)

In an international collaboration, Dr. Meng investigated CAR-T therapy holds great promise for solid tumors but is limited by the hostile tumor microenvironment and unstable target antigens. We developed an mRNA therapy that programs host immune cells in vivo to express a FAP-targeting CAR and attack cancer-associated fibroblasts. In multiple solid tumor models, this strategy—enhanced by chemotherapy and checkpoint blockade—drove strong tumor regression and long-lasting immune memory. The modified CAR mRNA boosted the speed and magnitude of responses, while inhibiting a cytokine pathway further relieved immunosuppression. Patient-derived xenografts revealed transcription factor network as biomarkers of resistance. These results show that a controllable, mRNA-based approach to remodeling the tumor stroma can unlock broader, more effective use of CAR-T therapy across solid cancers.

Deficiencies in methionine, tryptophan, and niacin remodels intestinal transcriptome and gut microbiota in mice (Scientific Reports, 2025)

In an international and academia–industry collaboration, Dr. Hara investigated the impact of essential amino acids on the gut microbiota in mice. While restriction of specific nutrients can recapitulate the benefits of caloric restriction, their intestinal effects remain poorly understood. Transient deprivation of methionine, tryptophan, and niacin reprogrammed oxidative phosphorylation pathways, expanded intestinal immune cells, and shifted gut microbial composition with increased Lactobacillus. These findings highlight nutrient restriction as a powerful lever to rewire host–microbiome interactions, offering fresh insights into cancer, inflammatory, autoimmune, neurodegenerative, and aging-related diseases.

N6-methyladenosine modification and significance in pancreatic cance (Cancer Med, 2025)

Dr. Hara highlighted the significance of RNA modifications in the diagnosis and therapy against solid cancers, indicating that the challenges and future optimization directions of this cancer medicine are explored, providing new perspectives and strategies for pancreatic cancer.

Antisense oligonucleotide targeting nicotinamide N-methyltransferase (Mol. Ther. Nuc. Acid., 2025)

In collaboration with Dr. Obika, Dr. Hara investigated antisense oligonucleotides targeting one-carbon metabolism in cancer as a novel molecular therapeutic strategy, which led to tumor inhibition.

データサイエンスが切り開く、新地平線
計算機を駆使した、
大容量解析と分子プロファイリング
高精度な予測が、豊かな未来医療を実現
阪大から発信！！