O100 Discovery of Novel Mutations and Fusion Proteins in Intrahepatic Cholangiocarcinoma

Sia, Daniela; Losic, Bojan; Cabellos, Laia; Revill, Kate; Bonal, Dennis M.; Hao, Ke; Miltiadous, Oriana; Zhang, Z.; Hoshida, Yoshihiko; Castillo, Miluska; Roayaie, Sasan; Thung, S N; Schwartz, Marc; Waxman, Samuel; Cordon‐Cardo, Carlos; Mazzaferro, V.; Schadt, Eric E.; Llovet, Josep M.

doi:10.1016/s0168-8278(14)60102-1

Cited by 2 publications

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“…Tumor genomic sequencing studies have identified the presence of FGFR2 fusion events in 14% to 45% of intrahepatic CCAs . These fusion events appear to occur mutually exclusive of KRAS and BRAF mutations and are capable of inducing malignant transformation in addition to imparting enhanced proliferative activity in established cancers .…”

Section: The Fibroblast Growth Factor Receptor (Fgfr) Pathwaymentioning

confidence: 99%

“…35 Tumor genomic sequencing studies have identified the presence of FGFR2 fusion events in 14% to 45% of intrahepatic CCAs. [36][37][38] These fusion events appear to occur mutually exclusive of KRAS and BRAF mutations and are capable of inducing malignant transformation in addition to imparting enhanced proliferative activity in established cancers. 36,39 CCAs harboring FGFR2 translocations also have distinct clinical and pathologic features, which include an intraductal or tubular anastomosing growth pattern and absence of stem-like markers and phenotype.…”

Section: The Fibroblast Growth Factor Receptor (Fgfr) Pathwaymentioning

confidence: 99%

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Role of the fibroblast growth factor receptor axis in cholangiocarcinoma

Ang

2015

J of Gastro and Hepatol

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Advanced cholangiocarcinoma (CCA) is a highly lethal disease with limited therapeutic options beyond cytotoxic chemotherapy. Molecular profiling of CCA has provided insights into the pathogenesis of this disease and identified potential therapeutic targets. The fibroblast growth factor receptor (FGFR) axis is important for maintaining tissue homeostasis. Aberrations in FGFR activity have been implicated in the development and progression of CCA and other malignancies, which has generated significant interest in exploring FGFR's therapeutic potential. FGFR2 fusion events are present in up to 17% of intrahepatic CCAs and appear to predict sensitivity to FGFR inhibitors even after progression on chemotherapy. These observations have led to a clinical trial evaluating FGFR inhibition in patients with CCA enriched for FGFR alterations. This review summarizes current knowledge about the role of the FGFR pathway in cholangiocarcinogenesis and ongoing work in developing FGFR-directed therapies as an antineoplastic strategy for CCA.

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Section: The Fibroblast Growth Factor Receptor (Fgfr) Pathwaymentioning

confidence: 99%