Exploring novel therapeutic targets in small bowel adenocarcinoma: insights from claudin 18.2, nectin-4, and HER3 expression analysis.

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with few established chemotherapy options and a dismal prognosis. We investigated the expression of claudin 18.2, nectin-4, human epidermal growth factor receptor 3 (HER3), and programmed death-ligand 1 (PD-L1) in SBA to identify potential antibody drug targets and analyzed associated clinicopathological features and prognosis.

Clinicopathological and molecular features of claudin-18 isoform 2 expression in patients with colorectal cancer: a single-center retrospective study.

Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.

Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database.

Purpose: Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined.

Response to Imatinib in a Patient With Gastric Adenocarcinoma With Q556_K558 In-Frame Deletion: A Case Report.

Imatinib may be a useful targeted agent for patients with advanced gastric adenocarcinoma who have KIT mutations.

Efficacy of anti-epidermal growth factor antibody rechallenge in RAS/BRAF wild-type metastatic colorectal cancer: a multi-institutional observational study.

Purpose: To investigate circulating tumor DNA (ctDNA) RAS mutant (MT) incidence before salvage-line treatment and the clinicopathological features and molecular biological factors associated with the efficacy of anti-epithelial growth factor receptor (EGFR) monoclonal antibody (mAb) rechallenge for tissue RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC).

Methods: This multi-institutional retrospective observational study included 74 patients with mCRC with tissue RAS/BRAF WT refractory to first-line chemotherapy containing anti-EGFR mAb. ctDNA RAS status was assessed using the OncoBEAM™ RAS CRC Kit.

Remarkable response to capmatinib in a patient with intrahepatic cholangiocarcinoma harboring - fusion.

Dysregulation of mesenchymal-epithelial transition factor () gene due to amplification, mutation, and fusion has been reported in various types of human cancers. Recently, the efficacy of small-molecule tyrosine kinase inhibitors (TKIs) targeting MET has been demonstrated in a wide range of -dysregulated tumors. The majority of biliary tract cancers including intrahepatic cholangiocarcinoma (iCCA) are diagnosed at an advanced stage, and the utility of conventional chemotherapy is limited.

Impact of immune checkpoint inhibitors on survival outcomes in advanced gastric cancer in Japan: A real-world analysis.

Background: Nivolumab was approved for the treatment of advanced gastric cancer in 2017 in Japan. The aim of this study was to assess the impact of nivolumab in a real-world clinical setting.

Methods: This single-institutional retrospective study included patients with advanced gastric or esophagogastric junction adenocarcinoma and a history of first-line chemotherapy with platinum-based doublet or triplet regimens between 2010 and 2020.

V600E-mutant colorectal cancer with CNS metastases treated successfully with encorafenib, binimetinib and cetuximab.

This report describes a case of BRAF V600E-mutated colorectal cancer with CNS metastases in which treatment with encorafenib, binimetinib and cetuximab was effective. There is limited information on the ability of encorafenib, binimetinib and cetuximab to enter the CNS.The patient was a 53-year-old man was diagnosed with ascending colon cancer (cT3N3M1c stage IVc).

CRP and soluble CTLA4 are determinants of anti-PD1 resistance in gastrointestinal cancer.

Targeting immune inhibitory checkpoint (IC) pathways have attracted great attention as a promising strategy for treating gastrointestinal (GI) cancer. However, the therapeutic efficacy is low in most cases, and little progress has been made in establishing biomarkers that predict the possible responses, and combination regimens that enhance the therapeutic efficacy. As a predictive biomarker, soluble forms of IC molecules have been recently highlighted.

Response to capmatinib in a patient with neuroendocrine carcinoma of the gallbladder origin harboring amplification.

Neuroendocrine carcinoma (NEC) of the gallbladder origin is particularly rare, accounting for only 0.38% of primary malignancies of the gallbladder, and standard therapies are limited. The gene encodes the tyrosine kinase receptor, c-Met.

Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma.

Background: Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population.

Retrospective Analysis of Definitive Chemoradiotherapy With FOLFOX in Patients With Esophageal Cancer Intolerant to Cisplatin.

Background/aim: Definitive chemoradiotherapy with cisplatin (CDDP) plus 5-fluorouracil is the standard treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC); however, CDDP is unsuitable for patients with cardiac and/or renal dysfunction. Based on the results of the PRODIGE5/ACCORD17 trial, 5-fluorouracil and leucovorin with oxaliplatin plus radiotherapy (FOLFOX-RT) has been recognized as a treatment option. However, the efficacy and safety of FOLFOX-RT is still unclear in Japan.

Bioactive TNIIIA2 Sequence in Tenascin-C Is Responsible for Macrophage Foam Cell Transformation; Potential of FNIII14 Peptide Derived from Fibronectin in Suppression of Atherosclerotic Plaque Formation.

One of the extracellular matrix proteins, tenascin-C (TN-C), is known to be upregulated in age-related inflammatory diseases such as cancer and cardiovascular diseases. Expression of this molecule is frequently detected, especially in the macrophage-rich areas of atherosclerotic lesions; however, the role of TN-C in mechanisms underlying the progression of atherosclerosis remains obscure. Previously, we found a hidden bioactive sequence termed TNIIIA2 in the TN-C molecule and reported that the exposure of this sequence would be carried out through limited digestion of TN-C by inflammatory proteases.

Dabrafenib and trametinib administration in patients with V600E/R or non-V600 mutated advanced solid tumours (BELIEVE, NCCH1901): a multicentre, open-label, and single-arm phase II trial.

Background: V600 mutations are common in melanoma, thyroid, and non-small-cell lung cancers. Despite dabrafenib and trametinib being standard treatments for certain cancers, their efficacy across various solid tumours remains unelucidated. The BELIEVE trial assessed the efficacy of dabrafenib and trametinib in solid tumours with V600E/R or non-V600 mutations.

Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial.

Background: Precision medicine has transformed cancer treatment by focusing on personalized approaches based on genomic abnormalities. However, comprehensive genomic profiling (CGP) and access to targeted therapies are limited in Japan. This study investigates the BELIEVE trial, which aims to improve drug accessibility for patients with actionable genetic abnormalities through off-label drug administration.

Progress report of a cross-organ and biomarker-based basket-type clinical trial: BELIEVE Trial.

Cancer genomic medicine using next-generation sequencers has been developing. However, the number of patients who could receive genomically matched therapy is limited because off-label use or patient-oriented compassionate use was not permitted under National Health Insurance in Japan. To improve patient drug accessibility, we initiated a biomarker-based basket-type clinical trial (NCCH1901) in October 2019 under patient-proposed healthcare services.

Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial).

Purpose: Mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) are positive predictive markers for immune checkpoint inhibitors. However, data on the activity of nivolumab in advanced dMMR/MSI-H rare cancers and more accurate biomarkers are worth exploring.

Patients And Methods: We conducted a multicenter phase II, open-label, single-arm clinical trial to explore the effectiveness and safety of nivolumab monotherapy in patients with advanced rare cancers with dMMR/MSI-H, in parallel with immune phenotype analysis, to explore new biomarkers.

A multi-institutional observational study evaluating the incidence and the clinicopathological characteristics of NeoRAS wild-type metastatic colorectal cancer.

Purpose: As circulating tumor DNA (ctDNA) measurement becomes more widespread, the "NeoRAS" phenomenon, where tissue rat sarcoma viral oncogene homolog (RAS) status converts from mutant (MT) to wild-type (WT) after treatment in metastatic colorectal cancer (mCRC), is gaining attention because ineffective epidermal growth factor receptor (EGFR) inhibitors may made effective. This study investigated its incidence and clinicopathological characteristics.

Patients And Methods: In total, 107 mCRC patients (refractory or intolerant to previous chemotherapies) with tissue RAS MT were enrolled in four institutions from June 2021 to August 2022.

A multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of ramelteon for the prevention of postoperative delirium in elderly cancer patients: a study protocol for JORTC-PON2/J-SUPPORT2103/NCCH2103.

Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns.

PDGF receptor signal mediates the contribution of Nestin-positive cell lineage to subcutaneous fat development.

The beiging of white adipose tissue (WAT) is expected to improve systemic metabolic conditions; however, the regulation and developmental origin of this process remain insufficiently understood. In the present study, the implication of platelet-derived growth factor receptor alpha (PDGFRα) was examined in the beiging of inguinal WAT (ingWAT) of neonatal mice. Using in vivo Nestin expressing cell (Nestin) lineage tracing and deletion mouse models, we found that, in the mice with Pdgfra gene inactivation in Nestin lineage (N-PRα-KO mice), the growth of inguinal WAT (ingWAT) was suppressed during neonatal periods as compared with control wild-type mice.

Progression patterns and site-specific responses in advanced gastric cancer patients treated with nivolumab.

Background: While the efficacy of immune checkpoint inhibitors (ICIs) reportedly varies among metastatic sites and progression patterns (classified as systemic progression [SP] or mixed progression [MP]), the clinical efficacy of ICIs against gastric cancer remains unclear. The response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer was investigated retrospectively.

Methods: Seventy-four advanced gastric cancer patients with measurable lesions who received nivolumab monotherapy between 2015 and 2020 were enrolled.