• Hedgehog-Wnt crosstalk in tumor-promoting cell competition (Dev Cell, 2026)

     

    The international collaboration demonstrated that intratumoral heterogeneity promotes cancer progression through interclonal communication. This study identifies a conserved Hh–Wnt signaling mechanism, enhancing invasion and tumor growth. The findings reveal Hh–Wnt crosstalk as a potential therapeutic vulnerability in heterogeneous cancers.

  • RNA Methyltransferase 3 Drives Pancreatic Acinar Cell Carcinoma Growth and Is a Therapeutic Target (STTT, 2026)

     

    In collaboration with our laboratory, Dr. Tatekawa and colleagues used KRAS-independent pancreatic acinar cell carcinoma (ACC) as a natural experiment to uncover METTL3-mediated m⁶A RNA methylation as a fundamental epitranscriptomic dependency of pancreatic tumorigenesis. Genetic and pharmacological inhibition of METTL3 induced rapid tumor apoptosis, highlighting METTL3 as a compelling therapeutic vulnerability and a potential target for combination chemoradiotherapy, while positioning ACC as a unique biological lens through which previously hidden dependencies of pancreatic cancer can be revealed.

  • 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.

  • In vivo engineered CAR-T cell therapy: lessons built from COVID-19 mRNA vaccines (Int J Mol Sci, 2025)

     

    In an academia-industry collaboration, Dr. Meng indicated the significance and implication of in vivo engineered CAR-T cell therapy. By bridging RNA-based technological insights, CAR-T therapy in vivo may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.

  • Recent exploration of cancer biomarkers hidden within urine or blood exosomes that provide fundamental information for future cancer diagnostics (Diagnostics, 2025)

     

    In academia-industry collaboration, Dr. Hara’s work focuses on the early detection of cancer, the mechanisms by which cancer cells evade growth controls such as contact inhibition, and the significance of early detection for effective treatment. The integration of next-generation sequencing technology for detailed gene expression analysis and the potential use of exosomes as cancer markers highlight the evolving approaches in cancer diagnostics.

  • Non-invasive detection of tumors by volatile organic compounds in urine (Biomedicines, 2025)

     

    In the academia-industry collaboration, Dr. Hara’s work focuses on the early detection of cancer, a leading cause of death that becomes increasingly difficult to treat as it progresses. Current blood biomarker tests have limitations in diagnosing early-stage cancer, highlighting the need for new biomarkers and diagnostic methods. This review examines recent advancements in cancer biomarker detection, particularly the analysis of volatile organic compounds (VOCs) in urine and the use of olfactory receptors.