FGFR Inhibitors: Clinical Activity and Development in the Treatment of Cholangiocarcinoma.

Abstract

PURPOSE OF REVIEW:

Cholangiocarcinoma is an aggressive cancer with a poor prognosis and limited treatment. Gene sequencing studies have identified genetic alterations in fibroblast growth factor receptor (FGFR) in a significant proportion of cholangiocarcinoma (CCA) patients. This review will discuss the FGFR signaling pathway's role in CCA and highlight the development of therapeutic strategies targeting this pathway.

RECENT FINDINGS:

The development of highly potent and selective FGFR inhibitors has led to the approval of pemigatinib for FGFR2 fusion or rearranged CCA. Other selective FGFR inhibitors are currently under clinical investigation and show promising activity. Despite encouraging results, the emergence of resistance is inevitable. Studies using circulating tumor DNA and on-treatment tissue biopsies have elucidated underlying mechanisms of intrinsic and acquired resistance. There is a critical need to not only develop more effective compounds, but also innovative sequencing strategies and combinations to overcome resistance to selective FGFR inhibition. Therapeutic development of precision medicine for FGFR-altered CCA is a dynamic process of involving a comprehensive understanding of tumor biology, rational clinical trial design, and therapeutic optimization. Alterations in FGFR represent a valid therapeutic target in CCA and selective FGFR inhibitors are treatment options for this patient population.

• Authors: Gentry King, Milind Javle
• Journal: Current oncology reports (Curr Oncol Rep) Vol. 23 Issue 9 Pg. 108 (07 16 2021) ISSN: 1534-6269 [Electronic] United States
• PMID: 34269915 (Publication Type: Journal Article, Review)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Aniline Compounds
• Morpholines
• Phenylurea Compounds
• Pyrazoles
• Pyrimidines
• Pyrroles
• Quinazolines
• Quinoxalines
• Receptors, Fibroblast Growth Factor
• futibatinib
• erdafitinib
• infigratinib
• derazantinib
• pemigatinib

Topics

• Aniline Compounds (therapeutic use)
• Bile Duct Neoplasms (drug therapy, genetics, metabolism)
• Bile Ducts, Intrahepatic (drug effects, metabolism, pathology)
• Cholangiocarcinoma (drug therapy, genetics, metabolism)
• Clinical Trials as Topic
• Humans
• Morpholines (therapeutic use)
• Mutation
• Phenylurea Compounds (therapeutic use)
• Precision Medicine (methods)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Pyrroles (therapeutic use)
• Quinazolines (therapeutic use)
• Quinoxalines (therapeutic use)
• Receptors, Fibroblast Growth Factor (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction (drug effects, genetics)