TY - JOUR
T1 - FGFR2 genomic aberrations
T2 - Achilles heel in the management of advanced cholangiocarcinoma
AU - Mahipal, Amit
AU - Tella, Sri Harsha
AU - Kommalapati, Anuhya
AU - Anaya, Daniel
AU - Kim, Richard
N1 - Funding Information:
RK has received honoraria from Bayer, Bristol Myer Squib (BMS) and Lilly for consulting; research funding from Bayer, BMS and Eisai. The other authors report no conflicts of interest for this work.
Publisher Copyright:
© 2019
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - ARQ 087
KW - BGJ398
KW - Cholangiocarcinoma
KW - FGFR
KW - Targeted therapy
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U2 - 10.1016/j.ctrv.2019.06.003
DO - 10.1016/j.ctrv.2019.06.003
M3 - Review article
C2 - 31255945
AN - SCOPUS:85067892384
SN - 0305-7372
VL - 78
SP - 1
EP - 7
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
ER -