eprintid: 10123796
rev_number: 19
eprint_status: archive
userid: 608
dir: disk0/10/12/37/96
datestamp: 2021-03-12 11:18:30
lastmod: 2022-05-09 13:34:30
status_changed: 2021-03-12 11:18:30
type: article
metadata_visibility: show
creators_name: Goyal, L
creators_name: Kongpetch, S
creators_name: Crolley, VE
creators_name: Bridgewater, J
title: Targeting FGFR inhibition in cholangiocarcinoma
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D19
divisions: G98
divisions: G99
keywords: Cholangiocarcinoma; Receptor, Fibroblast Growth Factor, Type 2; Cancer; Oncogenes; Chronic liver disease
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which are often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications have been identified in almost half of CCAs, in particular in intrahepatic CCA (iCCA), the subtype arising from bile ducts within the liver. Among patients with CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur almost exclusively in iCCA, where they are estimated to be found in up to 10–15% of patients. Clinical trials for selective FGFR kinase inhibitors have shown consistent activity of these agents in previously treated patients with iCCA harbouring FGFR alterations. Current FGFR kinase inhibitors show differences in their structure, mechanisms of target engagement, and specificities for FGFR1, 2, 3 and 4 and other related kinases. These agents offer the potential to improve outcomes in FGFR-driven CCA, and the impact of variations in the molecular profiles of the FGFR inhibitors on efficacy, safety, acquired resistance mechanisms, and patients’ health-related quality of life remains to be fully characterized. The most common adverse event associated with FGFR inhibitors is hyperphosphatemia, an on-target off-tumour effect of FGFR1 inhibition, and strategies to manage this include dose adjustment, chelators, and the use of a low phosphate diet. As FGFR inhibitors and other targeted agents enter the clinic for use in FGFR-driven CCA, molecular testing for actionable mutations and monitoring for the emergence of acquired resistance will be essential.
date: 2021-04
date_type: published
publisher: Elsevier BV
official_url: http://doi.org/10.1016/j.ctrv.2021.102170
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1852671
doi: 10.1016/j.ctrv.2021.102170
lyricists_name: Bridgewater, John
lyricists_name: Crolley, Valerie
lyricists_id: JABRI52
lyricists_id: VCROL16
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Cancer Treatment Reviews
volume: 95
article_number: 102170
citation:        Goyal, L;    Kongpetch, S;    Crolley, VE;    Bridgewater, J;      (2021)    Targeting FGFR inhibition in cholangiocarcinoma.                   Cancer Treatment Reviews , 95     , Article 102170.  10.1016/j.ctrv.2021.102170 <https://doi.org/10.1016/j.ctrv.2021.102170>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10123796/1/1-s2.0-S0305737221000189-main.pdf