Publications by authors named "Yusuke Tachibana"

The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated.

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We previously reported that combined therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib and AXL inhibitor ONO-7475 is effective in preventing the survival of drug-tolerant cells in high-AXL-expressing EGFR-mutated non-small cell lung cancer (NSCLC) cells. Nevertheless, certain residual cells are anticipated to eventually develop acquired resistance to this combination therapy. In this study, we attempted to establish a multidrug combination therapy from the first-line setting to overcome resistance to this combination therapy in high-AXL-expressing EGFR-mutated NSCLC.

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Article Synopsis
  • Lazertinib is a new drug effective for treating EGFR-mutant lung cancer, but resistance to it often develops, leading researchers to seek new treatment combinations.
  • The study found that targeting AXL can reduce lung cancer cell survival when combined with lazertinib, as AXL activation plays a role in resistance to the drug.
  • Further, using a triple therapy approach that includes AXL inhibitors and MCL-1 or YAP inhibitors alongside lazertinib significantly decreases cell viability and boosts cell death, showing promise in overcoming lazertinib resistance.
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Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC).

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Recently, novel Kirsten rat sarcoma viral oncogene homolog (KRAS) inhibitors have been clinically developed to treat KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, achieving complete tumor remission is challenging. Therefore, the optimal combined therapeutic intervention with KRAS G12C inhibitors has a potentially crucial role in the clinical outcomes of patients.

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It is recommended to get the multiple coronavirus disease 2019 (COVID-19) vaccinations for almost all people including asthma patients. A 70-year-old Japanese woman with asthma experienced worsening of respiratory symptoms after the second dose of the mRNA-based COVID-19 vaccine BNT162b2. The patient had hypercapnic respiratory failure and cardiac-apex ballooning and was diagnosed with takotsubo cardiomyopathy induced by asthma exacerbation.

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Article Synopsis
  • Patients with advanced non-small cell lung cancer and EGFR mutations received either immunochemotherapy (ABCP) or standard chemotherapy after failing initial TKI treatment in this study conducted in Japan.
  • Analysis of 57 patients revealed similar median progression-free survival (PFS) and overall survival (OS) between the two treatment groups, with no significant differences except in PD-L1-negative patients where ABCP performed worse.
  • The study suggests that the use of immunochemotherapy should be evaluated cautiously, particularly for those who are PD-L1-negative.
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Purpose: The effect of immuno-chemotherapy on patients with advanced non-small-cell lung cancer (NSCLC) harboring oncogenic mutations remains poorly understood. This study aimed to characterize the efficacy of immuno-chemotherapy and determine the optimal treatment strategy for such patients.

Methods: We conducted this retrospective cohort study on patients with NSCLC harboring oncogenic driver alterations and treated with an immune checkpoint inhibitor combined with chemotherapy at five institutions.

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Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies.

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The prognoses of patients with non-small-cell lung cancer (NSCLC) harboring () gene rearrangement have dramatically improved with the use of ALK tyrosine kinase inhibitors. Although immunological and nutritional markers have been investigated to predict outcomes in patients with several cancers, their usefulness in targeted therapies is scarce, and their significance has never been reported in patients receiving first-line treatment with alectinib. Meanwhile, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) has been investigated during crizotinib treatment.

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Background: The management of severe asthma-associated symptoms is essential since they are distressing to the affected patients, and also greatly impair their quality of life. Dupilumab, a monoclonal antibody, blocks interleukin (IL)-4 and IL-13 signaling, both of which are crucial in acquired and innate immunity pathways through fast signal transduction, leading to an early response to treatment. Although rapid improvement within 1-3 days after dupilumab treatment was observed in moderate-to-severe atopic dermatitis, an early response within 7 days of dupilumab treatment in severe asthma has not been reported.

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Background: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT.

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Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare-thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment.

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Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), in combination with carboplatin and etoposide (CE) chemotherapy. However, SCLC treatment options after progression to first-line chemotherapy are limited, warranting the readministration of previously used drugs. In combination with atezolizumab, CE readministration may theoretically be effective, based on two tentative mechanisms: its additive and synergistic effects on cytotoxic chemotherapy.

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