Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.

The addition of aPD1 to 5-FU/platinum in advanced gastric cancer (GC) yields variable responses. To understand cooperativity between chemotherapy and immunotherapy, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA- and TCR-sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients.

Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications.

Background: is one of the most frequently mutated oncogenes in humans. aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes.

Objectives: We identified features of genetic alterations in , including single amino acid substitutions and amplifications, based on the results of next-generation sequencing tests in 1667 advanced solid tumor patients.

Angiogenesis gene signatures in patient-derived tumor spheroids for genetic and tumor angiogenesis profiling.

: gastric cancers are highly vascular tumors, with elevated pro-angiogenic factors correlating with a poor prognosis. Despite advancements in precision medicine, there remains a critical need for platforms capable of identifying patient-specific therapeutic vulnerabilities. In this study, we present a 3D-printed patient-specific tumor angiogenesis chip that integrates genetic data to evaluate the molecular and functional characteristics of tumor angiogenesis in tumor spheroids derived from patients with gastric cancer.

Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach.

Background: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.

Changes in Cancer Care for Patients Aged 80 and Above: A Cohort Study from Samsung Comprehensive Cancer Center in South Korea.

With an estimated 70% of new cancer diagnoses expected to be in older adults within the next decade, cancer care for this population has attracted increasing global attention. Additionally, older patients are less likely to receive optimal cancer treatments. This retrospective cohort study utilized data from the Samsung Medical Center Cancer Registry, which includes patients diagnosed with cancer between 2008 and 2022.

Surgery or chemotherapy first? Unveiling the best approach for colorectal cancer with resectable liver metastasis.

Background: Although neoadjuvant chemotherapy is foundational in treating stage IV colorectal cancer, its effectiveness for patients with resectable colorectal cancer liver metastasis is still under debate. This study evaluates the oncologic outcomes of operation-first compared with chemotherapy-first strategies in patients with initially resectable synchronous colorectal cancer liver metastasis, including the effects of targeted therapy and the survival outcomes after recurrence based on treatment strategy.

Methods: We conducted a retrospective analysis of 336 patients with resectable synchronous colorectal cancer liver metastasis who underwent complete radical resection and perioperative chemotherapy between 2007 and 2022.

Zanidatamab monotherapy or combined with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma: a phase 1 trial.

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine).

Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies.

Purpose: The Cancer Genome Atlas (TCGA) classifies gastric cancer (GC) into four molecular subtypes: Epstein-Barr virus-positive, microsatellite instability-high (MSI-H), genomically stable (GS), and chromosomal instability (CIN). This exploratory analysis compared the genomic landscape of late-stage GC from KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 studies with early-stage GC from TCGA and evaluated the genomic characteristics of late-stage GC in patients of Western and Asian origin.

Materials And Methods: Using pretreatment tumor samples, bulk DNA was analyzed via whole-exome sequencing (WES; KEYNOTE-059/KEYNOTE-061) and FoundationOneCDx (KEYNOTE-062) to determine TCGA-defined molecular subtypes (only MSI-H is determinable from FoundationOneCDx), genomic alterations, homologous recombination deficiency (HRD), and tumor mutational burden (TMB); gene expression signatures were analyzed using RNA sequencing.

Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.

Purpose: Adding pembrolizumab to first-line fluoropyrimidine (5-FU)/platinum chemotherapy plus trastuzumab improves outcomes in advanced HER2+ gastroesophageal adenocarcinomas, but the benefit is largely confined to dual HER2+ and PD-L1+ patients. To assess the contributions of components, we conducted a phase II trial evaluating 5-FU/platinum/trastuzumab and added pembrolizumab in cycle 2 in patients with metastatic HER2+ disease.

Patients And Methods: Treatment-naïve patients with advanced HER2+ gastroesophageal cancer underwent a baseline biopsy and received a single dose of 5-FU/platinum with trastuzumab followed by repeat biopsy.

Epidermal Growth Factor Receptor Aberrations Identified by Next-generation Sequencing in Patients with Metastatic Cancers.

Purpose: The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.

Materials And Methods: We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center.

Association of ATM and ARID1A in gastric carcinoma.

Background: The ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear.

Phase 2 trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (EAGLES, Korean Cancer Study Group UN18-09).

Background: In this single-arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first-line chemotherapy.

Methods: Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR).

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

Background: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.

CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells.

Background: In v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant colorectal cancer (CRC), encorafenib-cetuximab has been established as standard second-line therapy, but not all patients respond and the duration of response is relatively short. Overcoming intrinsic or acquired resistance to BRAF/EGFR inhibitors is crucial for enhancing treatment outcomes in metastatic BRAF-mutated CRC. The aim of the study is to investigate the resistance mechanisms in BRAF-mutant CRC patient refractory to BRAF/EGFR targeted therapy.

Imatinib in c-KIT-mutated metastatic solid tumors: A multicenter trial of Korean Cancer Study Group (UN18-05 Trial).

Introduction: We conducted an open-label, single-arm, multi-center phase II trial to evaluate the efficacy and safety of imatinib chemotherapy-refractory or metastatic solid tumor patients with c-KIT mutations and/or amplification.

Methods: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

Purpose: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF.

Materials And Methods: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME).

The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial.

Minnelide is a water-soluble disodium salt variant of triptolide, an HSP70 inhibitor that can prevent tumor progression and induce apoptosis. Maximum tolerated dose (MTD), safety, and antitumor activity of Minnelide alone and its combination with paclitaxel were evaluated in this open-label, single-center, dose-escalation phase I study (NCT05566834) in patients who were previously treated for advanced gastric cancer (AGC). Minnelide was administered orally using a 3 + 3 dose-escalation design as monotherapy (Regimen A), and in combination with paclitaxel (Regimen B & C).

Stool Protein Mass Spectrometry Identifies Biomarkers for Early Detection of Diffuse-type Gastric Cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls.