A5086218839- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Neuroendocrine Tumor Research Advances
- Histone Deacetylase Inhibitors Research
- Colorectal Cancer Treatments and Studies
- Pancreatitis Pathology and Treatment
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Occupational and environmental lung diseases
- Cancer Cells and Metastasis
- Gastrointestinal motility and disorders
- MicroRNA in disease regulation
- Gastric Cancer Management and Outcomes
- Radiomics and Machine Learning in Medical Imaging
- Peptidase Inhibition and Analysis
Kyoto Prefectural University of Medicine
2006-2025
Daiichi-Sankyo (South Korea)
2024
Eli Lilly (United States)
2024
Boehringer Ingelheim (United States)
2024
Chugai Pharma (United States)
2024
Daiichi Sankyo (Germany)
2024
Kanazawa University
2013-2023
Kanazawa Medical University
2009-2023
Kyoto first Red Cross hospital
2023
Shionogi (United States)
2016-2021
Lung cancers with epidermal growth factor receptor (EGFR)-activating mutations show good clinical response to gefitinib and erlotinib, selective tyrosine kinase inhibitors (TKI) EGFR, but these tumors invariably develop drug resistance. Host stromal cells have been found a considerable effect on the behavior of cancer cells. Little is known, however, about role host sensitivity TKIs. We therefore assessed crosstalk between lung harboring EGFR susceptibility EGFR-TKIs.We evaluated...
A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated was associated EGFR HER3 maintaining cell survival inducing the emergence of cells tolerant inhibition reduced viability cancer overexpressing were exposed The addition during either...
BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family. upregulation required for apoptosis induction by EGF receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in EGFR-mutant forms non-small cell lung cancer (NSCLC). Notably, deletion polymorphism occurs naturally 12.9% East Asian individuals, impairing generation isoform EGFR-TKIs gefitinib and erlotinib therefore conferring an inherent drug-resistant phenotype. Indeed, patients with NSCLC, who harbored this host...
Cancer cell microenvironments, including host cells, can critically affect cancer behaviors, drug sensitivity. Although crizotinib, a dual tyrosine kinase inhibitor (TKI) of ALK and Met, shows dramatic effect against EML4-ALK lung these cells acquire resistance to crizotinib by several mechanisms, amplification gatekeeper mutation. We determined whether microenvironmental factors trigger in cells.We tested the effects ligands produced endothelial fibroblasts, themselves, on susceptibility...
Abstract Purpose: Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non–small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial intervention crucial prolonged survival of these patients. The activation anexelekto (AXL) signaling known be associated intrinsic and EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated best combat AXL-induced tolerance...
Abstract Background Treatment with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) leads to initial response in most patients EGFR ‐mutated non‐small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation NSCLC mutations who exhibit clinical outcomes that require treatment immune checkpoint (ICIs). Therefore, identify eligible cases treat ICIs, we retrospectively analyzed correlation between features and efficacy ICIs mutations. Patients Methods...
Abstract Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show while AXL-low expressing EGFR mutated lung cancer ( mut-LC) cells are more sensitive osimertinib than AXL-high mut-LC cells, a small population emerge tolerance. The mediated by increased expression and phosphorylation of insulin-like factor-1 receptor (IGF-1R), caused...
Abstract Mutations in the ALK gene are detectable approximately 40% of ALK-rearranged lung cancers resistant to inhibitors. Although epithelial-to-mesenchymal transition (EMT) is a mechanism resistance various targeted drugs, its involvement inhibitor largely unknown. In this study, we report that both ALK-mutant L1196M and EMT were concomitantly detected single crizotinib-resistant lesion patient with cancer. Digital PCR analyses combined microdissection after IHC staining for markers...
Secondary sarcopenia is defined as a decrease in muscle mass due to disease or malnutrition. Several studies have reported that secondary an indicator of postoperative recurrence. We hypothesized there correlation between the effect immune checkpoint inhibitors (ICIs) and sarcopenia. retrospectively analyzed 38 patients with advanced non-small cell lung cancer (NSCLC) who were treated ICIs February 2016 April 2018. Patients divided into two groups according change rate psoas major area...
Background: Cancer immunotherapy is being developed as a promising alternative for advanced non-small cell lung cancer (NSCLC). However, novel biomarkers are required to select patients that will benefit from treatment with immune checkpoint inhibitors (ICIs) long period of time. The gut microbiome expected be biomarker ICI response owing the regulation status within host.
Abstract Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer. However, the responders acquire resistance almost without exception. We recently reported that hepatocyte (HGF) induces EGFR-TKI by activating MET restores downstream mitogen activated protein (MAPK)/extracellular signal regulated (ERK)1/2 phosphoinositide 3-kinase (PI3K)/Akt signaling. The purpose of this study was...
Abstract Purpose: The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the most frequent cause of acquired resistance to reversible EGFR tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib, lung cancer. Irreversible EGFR-TKIs are expected overcome EGFR-TKI cancer harboring EGFR. However, it clear that may also develop this class inhibitors. We showed previously hepatocyte (HGF) induced EGFR-activating mutations. Here, we investigated whether HGF irreversible...
Abstract Purpose: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal receptor–tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer cells by activating Met the downstream phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, continuous exposure HGF accelerates emergence of EGFR-TKI–resistant clones. We assayed whether a new inhibitor, E7050, which is currently being evaluated clinical trials, could overcome these three mechanisms...
Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI) erlotinib and gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation, Met amplification, HGF overexpression, thereafter relapsing. Thus, it is urgent to develop novel agents overcome EGFR-TKI resistance. We tested of mutant-selective WZ4002 Met-TKI E7050 on 3 cancer cell lines different mechanisms: PC-9/HGF cells with an...
Abstract The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in patients with opioid-induced constipation and chronic noncancer pain 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo 623). primary endpoint summary measures treatment-emergent adverse events (AEs). Additional endpoints included opioid...
Abstract Purpose: The BIM deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non–small cell lung cancer (NSCLC) harboring mutations. Here, we investigated whether the contributes against osimertinib, a third-generation EGFR-TKI. In addition, determined efficacy of histone deacetylase (HDAC) inhibitor, vorinostat, this form elucidated underlying mechanism. Experimental Design: We used EGFR-mutated...
Abstract EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin TKI has been previously reported, however, the precise mechanism by which activation contributes to is not clear. Here, we show that inhibition results signaling a Notch3-dependent manner, facilitates survival subset cells call “adaptive persisters”. We reported EGFR-TKI treatment rapidly activates Notch3, and here describe physical...
Little is known regarding the effectiveness and tolerability of immune checkpoint inhibitor (ICI) rechallenge after disease progression following initial ICI treatments. To identify eligible patients for rechallenge, we retrospectively analyzed relationship between clinical profiles effect in with non-small cell lung cancer (NSCLC). We enrolled 35 NSCLC at six different institutions who were retreated ICIs discontinued treatments due to progression. Cox proportional hazards models used...
Abstract Epithelial–mesenchymal transition (EMT)—a fundamental process in embryogenesis and wound healing—promotes tumor metastasis resistance to chemotherapy. While studies have identified signaling components transcriptional factors responsible the TGF-β-dependent EMT, whether how intracellular metabolism is integrated with EMT remains be fully elucidated. Here, we showed that TGF-β induces reprogramming of amino acid metabolism, which necessary promote non-small cell lung cancer cells....
Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated significantly better survival outcomes than alone in patients advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The nutritional index (PNI) (LIPI) biomarkers inhibitor (ICI) monotherapy or chemotherapies. Thus, we aimed to examine whether these factors could also be We retrospectively examined 237 NSCLC treated In...