Kyoto University · Medicine
Professor Yuji Eso's research lab focuses on the molecular mechanisms underlying hepatocellular carcinoma (HCC) and colorectal cancer, with a central emphasis on DNA repair pathways, microsatellite instability (MSI), and tumor immune microenvironment. The lab investigates how chronic inflammation and genetic alterations, such as MSH2 deficiency and AID expression, contribute to genomic instability and tumorigenesis. A key research direction involves evaluating the predictive biomarkers and treatment response to molecular targeted therapies (e.g., lenvatinib) and immune checkpoint inhibitors (ICIs), particularly in relation to systemic factors like NLR and pharmacokinetic metrics such as 2M-DBR. The lab also explores the translational potential of MSI and tumor mutation burden (TMB) as pan-cancer biomarkers for immunotherapy response.
Figures are computed from collected data and may differ slightly.
Recent innovations in the next-generation sequencing technologies have unveiled that the accumulation of genetic alterations results in the transformation of normal cells into cancer cells. Accurate and timely repair of DNA is, therefore, essential for maintaining genetic stability. Among various DNA repair pathways, the mismatch repair (MMR) pathway plays a pivotal role. MMR deficiency leads to a molecular feature of microsatellite instability (MSI) and predisposes to cancer. Recent studies rev
Systemic chemotherapy using a multitargeted tyrosine kinase inhibitor is an established treatment for advanced-stage tumors in various organs. Comprehensive genomic analyses using next-generation sequencing technology revealed the intra- and intertumor heterogeneity of human hepatocellular carcinomas (HCCs), and provided evidence for the use of therapeutic agents effective against multiple targets in tumor cells. Recently, the efficacy and safety of a multitargeted tyrosine kinase inhibitor, len
The development of immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death protein ligand 1 (PD-L1) has revolutionized the treatment strategy in various types of cancers. In addition, recent studies have revealed that tumor microsatellite instability (MSI) status and tumor mutation burden (TMB) contribute significantly to the therapeutic response to anti-PD-1 monoclonal antibody (mAb), which led to
The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC.
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via NF-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2(-) (/) (-)AID(+), ALB-MSH2(-) (/) (-), and ALB-AID
Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 d
Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a treatment switch to tyrosine kinase inhibitors (TKIs) needs to be considered. However, TACE could worsen liver function, thereby narrowing the time window for a switch to TKIs because TKIs are recommended for patients with Child-Pugh grade A (CP-A). We investigated the factors associated with CP grade deterioration afte
SEUS guidance is recommended for more accurate localization of suitable hepatic lesion biopsy areas as it increases conspicuity and differentiates viable areas from denaturalization or necrosis.
Immunotherapy with immune checkpoint inhibitors has been shown to be beneficial for cancers originating from various organs. In May 2020, combination therapy with anti-programmed death-ligand 1 antibody atezolizumab and anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was approved as a novel first-line systemic therapy for hepatocellular carcinoma (HCC). The number of patients with HCC not caused by hepatitis virus infection (non-viral HCC), including non-alcoholic steatohepat
Serum M2BPGi levels are correlated with nutritional status markers in patients with CLD and could be a useful clinical marker of malnutrition.
US-guided polidocanol foam sclerotherapy may be an effective and safe method for the treatment of symptomatic giant hepatic cysts.
Our findings suggest that US-guided liver tumor biopsy is a useful and safe method for obtaining high-quality samples for NGS-based clinical sequencing. In cases with metastatic liver tumors, US-guided biopsy should be considered to provide accurate and optimal sequencing results for patients.
Baseline M2BPGi levels may predict the tolerability and treatment response to lenvatinib. Patients with high M2BPGi levels may less likely to benefit from lenvatinib therapy.
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