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http://dx.doi.org/10.1200/JCO.2012.47.7521 | DOI Listing |
Cell Genom
September 2025
Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance.
View Article and Find Full Text PDFCancer Res Commun
September 2025
Spanish National Cancer Research Centre, Madrid, Madrid, Spain.
Purpose: Advanced, pre-treated TNBC has a dismal prognosis and lacks effective options beyond standard cytotoxics. We previously showed, via phosphoproteomic screening, that CDK6 and ERK hyperactivation are linked to adverse outcomes and represent actionable targets. This prompted us to evaluate palbociclib and binimetinib in advanced TNBC after one or two prior therapies.
View Article and Find Full Text PDFFront Immunol
September 2025
Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Background: Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by a gain-of-function mutation in the gene, which regulates inflammasome-mediated interleukin-1β (IL-1β) production. This leads to recurrent episodes of fever, rash, and arthritis, typically beginning in childhood.
Objective: To demonstrate the role of a missense mutation, c.
Int J Surg Pathol
September 2025
Department of Pathology, The Thirteenth People's Hospital of Chongqing, Chongqing, China.
Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal cells. Recent advancements in genomic profiling have identified novel gene fusions in these tumors, offering new insights into their pathogenesis and potential therapeutic targets. Here, we describe a spindle cell sarcoma harboring a novel gene fusion.
View Article and Find Full Text PDFBrief Bioinform
August 2025
Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, China.
Accurate tumor mutation burden (TMB) quantification is critical for immunotherapy stratification, yet remains challenging due to variability across sequencing platforms, tumor heterogeneity, and variant calling pipelines. Here, we introduce TMBquant, an explainable AI-powered caller designed to optimize TMB estimation through dynamic feature selection, ensemble learning, and automated strategy adaptation. Built upon the H2O AutoML framework, TMBquant integrates variant features, minimizes classification errors, and enhances both accuracy and stability across diverse datasets.
View Article and Find Full Text PDF