Rationale for targeting fibroblast growth factor receptor signaling in breast cancer

Breast Cancer Res Treat. 2015 Feb;150(1):1-8. doi: 10.1007/s10549-015-3301-y. Epub 2015 Feb 13.

Abstract

Fibroblast growth factor receptor (FGFR) signaling is involved in multiple biological processes, including cell proliferation, survival, differentiation, migration, and apoptosis during embryonic development and adult tissue homeostasis. Given its role in the activation of critical signaling pathways, aberrant FGFR signaling has been implicated in multiple cancer types. A comprehensive search of PubMed and congress abstracts was conducted to identify reports on FGFR pathway components in breast cancer. In breast cancers, FGFR1 and FGFR4 gene amplification and single nucleotide polymorphisms in FGFR2 and FGFR4 have been detected. Commonly, these FGFR aberrations and gene amplifications lead to increased FGFR signaling and have been linked with poor prognosis and resistance to breast cancer treatments. Here, we review the role of FGFR signaling and the impact of FGFR genetic amplifications/aberrations on breast tumors. In addition, we summarize the most recent preclinical and clinical data on FGFR-targeted therapies in breast cancer. Finally, we highlight the ongoing clinical trials of the FGFR-targeted agents dovitinib, AZD4547, lucitanib, BGJ398, and JNJ-42756493, which are selected for patients with FGFR pathway-amplified breast cancer. Aberrant FGFR pathway amplification may drive some breast cancers. Inhibition of FGFR signaling is being explored in the clinic, and data from these trials may refine our ability to select patients who would best respond to these treatments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Genetic Variation
  • Humans
  • Molecular Targeted Therapy*
  • Mutation
  • Prognosis
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use*
  • Quinoxalines / pharmacology*
  • Quinoxalines / therapeutic use*
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction / drug effects*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Pyrazoles
  • Quinoxalines
  • Receptors, Fibroblast Growth Factor
  • erdafitinib