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Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFA safe haven for cancer cells: tumor plus stroma control by DYRK1B.
Oncogene
January 2025
Department of Gastroenterology, Endocrinology and Metabolism, Center for Tumor and Immune Biology, Philipps University Marburg, Marburg, Germany.
The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.
View Article and Find Full Text PDFLongitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFSupramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.
Nat Commun
January 2025
College of Chemistry, Nankai University, Tianjin, China.
Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria.
View Article and Find Full Text PDFGlobal insight into rare disease and orphan drug definitions: a systematic literature review.
BMJ Open
January 2025
Centre for Public Health, Institute of Clinical Sciences B, Royal Victoria Hospital, Queen's University Belfast School of Medicine, Dentistry and Biomedical Sciences, Belfast, UK.
Objectives: This study sheds light on the available global definitions, classifications, and criteria used for rare diseases (RDs), ultrarare diseases (URDs), orphan drugs (ODs) and ultraorphan drugs (UODs) and provides insights into the rationale behind these definitions.
Design: A systematic literature review was conducted to identify existing definitions and the criteria used to define RDs, ODs and their subtypes.
Data Sources: Searches were performed in the PubMed/Medline, Embase, Scopus and Web of Science (Science and Social Sciences Citation Index) databases covering articles published from 1985 to 2021.
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