Cholangiocarcinoma (CCA) is the second most frequent primary liver cancer, following hepatocellular carcinoma (HCC). Progress in the molecular understanding of CCA has led to the development of several agents, including FGFR inhibitors, such as pemigatinib, whose approval has marked a new era in this hepatobiliary malignancy. However, a number of questions remain unanswered, including the development of secondary resistance and the role of combination therapies, including FGFR inhibitors. Herein, we specifically focus on the current challenges and future research directions of pemigatinib use in CCA patients.
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http://dx.doi.org/10.3390/curroncol29100626 | DOI Listing |
Biomolecules
December 2024
Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA.
Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions.
View Article and Find Full Text PDFExplor Target Antitumor Ther
November 2024
Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), 6500 Bellinzona, Switzerland.
Advanced urothelial carcinoma (aUC) has a dismal prognosis, with a 5-year survival rate of approximately 10%. Platinum-based chemotherapy has been the backbone of the first-line treatment of aUC for over 40 years. Only in the last decade, the treatment of aUC has evolved and been enriched with new classes of drugs that demonstrated pivotal improvements in terms of oncological responses and, ultimately, survival.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czechia.
Impaired fibroblast growth factor receptor (FGFR) signaling is associated with many human conditions, including growth disorders, degenerative diseases, and cancer. Current FGFR therapeutics are based on chemical inhibitors of FGFR tyrosine kinase activity (TKIs). However, FGFR TKIs are limited in their target specificity as they generally inhibit all FGFRs and other receptor tyrosine kinases.
View Article and Find Full Text PDFCancer Prev Res (Phila)
January 2025
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
The study by Downs and colleagues targets patients with non-muscle-invasive bladder cancer (NMIBC) to explore secondary/tertiary cancer prevention strategies. Utilizing a "window-of-opportunity" design, erlotinib was evaluated for its effect on EGFR phosphorylation, although the unconventional dosing regimen failed to demonstrate efficacy. New opportunities in NMIBC prevention include targeting FGFR3 mutations with emerging FGFR inhibitors.
View Article and Find Full Text PDFBioorg Chem
December 2024
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs.
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