FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma |
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| Affiliation: | 1. Department of Medical Oncology, Mayo Clinic, Rochester, MN, United States;2. Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, SC, United States;3. Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, United States;1. Cleveland Clinic Foundation, Cleveland, OH, USA;2. Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;3. Deccan College of Medical sciences, India;4. Carol Davila University of Medicine and Pharmacy, Romania;5. Faculty of Medicine, Damascus University, Syria;6. Ascension St. John Hospital, Michigan, USA;7. Department of Hematology and Oncology, Mayo Clinic, AZ, USA;1. Department of Medical Oncology, Catalan Institute of Oncology (ICO), Girona, Spain; Girona Biomedical Research Institute (IDIBGi), Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain;3. Nanomedicine and Biotechnology Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;4. Department of Medical Oncology, Centro Hospitalar do Porto, Porto, Portugal;5. Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy;6. Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Edegem, Antwerp, Belgium;7. Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX, USA;1. Department of Surgery, University of Washington Medical Center, Seattle, WA, USA;2. Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA;1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA;2. Weill Medical College, Cornell University, New York, NY, USA;3. Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA;4. Gustave Roussy, Villejuif, France;5. Providence Cancer Center Oncology and Hematology Care Clinic, Portland, OR, USA;6. Digestive Molecular Clinical Oncology Unit, University of Verona, Verona, Italy;7. University of Kansas Cancer Center, Kansas City, KS, USA;8. Baylor Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA;9. Mayo Clinic Cancer Center, Phoenix, AZ, USA;10. Morristown Memorial Hospital, Carol Cancer Center, Morristown, NJ, USA;11. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA;12. Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea;13. Fox Chase Cancer Center, Philadelphia, PA, USA;14. University of Chicago Medicine, Chicago, IL, USA;15. University Hospitals Gasthuisberg, Leuven, Belgium;p. Clinical Digestive Oncology, KU Leuven, Leuven, Belgium;q. Incyte Corporation, Wilmington, DE, USA;r. Hannover Medical School, Hannover, Germany |
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| Abstract: | Cholangiocarcinoma is the most common aggressive biliary tract malignancy with dismal prognosis. Though surgical resection of the primary tumors yields better prognosis, majority of patients present at advanced, inoperable stages rendering systemic therapy as the only option. A significant progress has been made in understanding the cholangiocarcinoma tumorigenesis and molecular markers over the last decade, which opens doors to precision medicine in this dismal cancer. Intrahepatic cholangiocarcinomas are most likely to harbor mutations in isocitrate dehydrogenase genes (IDH1, IDH2), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3), Eph receptor 2 (EPHA2), and BAP1 (gene involved in chromatin remodeling) genes, whereas ARID1B, ELF3, PBRM1, cAMP dependent protein kinase (PRKACA, and PRKACB) genetic mutations were implicated more commonly in distal and perihilar subtypes. Genomic studies have shown that FGFR2 aberrations are implicated in approximately 15% of intrahepatic cholangiocarcinomas, which make FGFR2 aberrations (Achilles heel) as potential novel targets in the management of cholangiocarcinoma. The current review comprehensively focuses on the role of FGFR2 inhibition either alone or in combination with other targeted therapy that act on down-stream and alternate kinase pathways in cholangiocarcinoma. |
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| Keywords: | Targeted therapy Cholangiocarcinoma BGJ398 ARQ 087 |
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