Cell
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Published: January 2004
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http://dx.doi.org/10.1016/s0092-8674(04)00049-2 | DOI Listing |
Cancer Cell
March 2025
Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorder Center and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans.
View Article and Find Full Text PDFInt J Biol Sci
March 2025
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), has been established as the first-line treatment for advanced hepatocellular carcinoma (HCC) because of its superior efficacy when in comparison with sorafenib. However, the inevitable development of drug resistance is a significant barrier to achieve a curative outcome and negatively impacts the prognosis. Therefore, it is imperative to delve into the mechanisms underlying lenvatinib resistance (LR) and to identify potential strategies for rational combination treatments.
View Article and Find Full Text PDFNat Commun
March 2025
Laboratory for Atomistic and Molecular Mechanics (LAMM), Massachusetts Institute of Technology, Cambridge, MA, USA.
Spongin is a fundamental biopolymer that has played a crucial role in the skeletogenesis of keratosan sponges for over 800 million years. This biomaterial had so far remained chemically unidentified and believed to be an enigmatic type of halogenated collagen-keratin-based bioelastomer. Here we show collagen I and III as the main structural components of spongin.
View Article and Find Full Text PDFMol Cell Proteomics
March 2025
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA. Electronic address:
Protein post-translational modifications have traditionally been challenging to identify due to their dynamic regulation and typically low stoichiometry. Methods for phosphopeptide enrichment from complex proteomes developed in the Hunt lab in the late 1990's and early 2000's launched the field of phosphoproteomics, the large-scale analysis of protein phosphorylation sites. To improve phosphopeptide tandem mass spectra and address the further challenge of identifying other labile PTMs such as glycosylation or tyrosine sulfation, the Hunt lab invented and disseminated electron transfer dissociation (ETD), a novel method for peptide and protein fragmentation.
View Article and Find Full Text PDFEur J Med Chem
March 2025
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products and Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, Yunnan, 650500, China. Electronic address:
Acquired resistance to tyrosine kinase inhibitors (TKIs) has become a significant challenge in cancer therapy, underscoring the urgent need for developing alternative therapeutic targets to relieve it. Targeting TGF-β signaling pathway has been emerging as a promising antitumor strategy due to its pivotal role in cancer progression and metastasis. Our previous study identified YR-290 as an anticancer molecule through inhibiting TGF-β signaling, but its poor solubility limited its subsequent development.
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