Through a clinical deep sequencing protocol, Wu and colleagues have identified multiple FGFR fusion proteins in diverse cancers. Pharmacologic inhibition of FGFR suppressed the growth of FGFR fusion-positive tumor models, suggesting that these FGFR fusions are oncogenic drivers and highlighting the use of streamlined clinical sequencing efforts to identify novel, actionable driver oncoproteins in human tumors.
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http://dx.doi.org/10.1158/2159-8290.CD-13-0185 | DOI Listing |
Calcif Tissue Int
January 2025
National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, 20892, USA.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by hypersecretion of fibroblast growth factor 23 (FGF23) by typically benign phosphaturic mesenchymal tumors (PMTs). FGF23 excess causes chronic hypophosphatemia through renal phosphate losses and decreased production of 1,25-dihydroxy-vitamin-D. TIO presents with symptoms of chronic hypophosphatemia including fatigue, bone pain, weakness, and fractures.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China.
Molecular glues are promising protein-degrading agents that hold great therapeutic potential but face significant challenges in rational design, effective synthesis, and precise targeting of tumor sites. In this study, we first overcame some of these limitations by introducing a fumarate-based molecular glue handle onto specific ligands of therapeutic kinases (TBK1, FGFR, and Bcr-Abl), resulting in the effective degradation of these important cancer targets. Despite the broad applicability of the strategy, we unexpectedly discovered potent and widespread cytotoxicity across various cell lines, including noncancerous ones, rendering it less effective in cancer therapy.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Background: FGFR2 fusions or rearrangements occur in 13%-20% of patients with intrahepatic cholangiocarcinoma (iCCA). Pemigatinib, a representative FGFR inhibitor, is commonly used for targeted therapy in such patients. Additionally, brain metastasis (BM) is extremely rare in advanced iCCA, and there is currently no standard treatment strategy for advanced iCCA patients with BM.
View Article and Find Full Text PDFMed
January 2025
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; WIN Consortium, Paris, France; University of Nebraska, Omaha, NE, USA. Electronic address:
Tumor-agnostic US Food and Drug Administration approvals are transforming oncology. They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAF mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms.
View Article and Find Full Text PDFBackground: Futibatinib is the only covalent inhibitor of FGFR1-4 to gain regulatory approval in oncology. In this article, we present genomic analyses of tissue biopsies and circulating tumor DNA (ctDNA) from patients with 1 of nearly 20 tumor types treated with futibatinib in the phase I/II FOENIX study.
Patients And Methods: Eligible patients included those with ctDNA samples collected per protocol at baseline and/or progression on futibatinib in the phase Ib portion of the study for FGF/FGFR-altered advanced solid tumors or the phase II portion of the study for FGFR2 fusion/rearrangement-positive cholangiocarcinoma.
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