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A Case of Non-Small Cell Lung Cancer with Mutually Exclusive and Mutations.
Curr Issues Mol Biol
January 2025
Department of Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, PA 19140, USA.
Historically, and mutations were believed to be mutually exclusive. However, over the past few years, there have been emerging case reports showing the co-existence of both mutations in a single case. The majority of these co-occurring alterations were detected in samples collected from patients with resistance to tyrosine kinase inhibitor (TKI) treatment, indicating a potential functional role in driving resistance to therapy.
View Article and Find Full Text PDFExploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.
Drug Resist Updat
January 2025
Loma Linda University Cancer Center, Loma Linda, CA 92354, United States; Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, United States. Electronic address:
Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.
View Article and Find Full Text PDFEvolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response.
Cancer Res
January 2025
Stanford University, Stanford, California, United States.
Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.
View Article and Find Full Text PDFRET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs.
Cancer Lett
January 2025
Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China.
Pralsetinib demonstrated impressive improvement of survival in non-small cell lung cancer (NSCLC) patients harbored de novo RET fusion. However, the efficacy in patients with acquired RET fusion after resistance to EGFR/ALK-TKIs has only been reported on a case-by-case basis, and the strategy for overcoming the acquired RET fusion has not been fully investigated. This multicenter, real-world analysis enrolled 32 patients with unresectable NSCLC harbored acquired RET fusion after resistance to EGFR/ALK-TKIs in 23 centers across China from July 1st, 2018 to Nov 23rd, 2022.
View Article and Find Full Text PDFConserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.
Cell Rep
January 2025
NDM Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK. Electronic address:
Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney.
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