Investigational drugs targeting fibroblast growth factor receptor in the treatment of non-small cell lung cancer

ABSTRACT

Introduction: Fibroblast growth factor receptor (FGFR) due to its central role in regulating cell survival, is a promising target for cancer therapeutics. Dysregulation of the FGFR pathway has been observed in several malignancies, including non-small cell lung cancer (NSCLC) particularly in patients with squamous histology.

Areas covered: The aim of this article is to review the most relevant findings of clinical trials investigating drugs targeting FGFR pathway: such as FGFR tyrosine kinase inhibitors (TKIs), FGFR monoclonal antibodies and FGF ligand traps in NSCLC patients.

Expert opinion: At present, clinical activity of drugs targeting FGFR in NSCLC is disappointing. Further studies are needed in order to better identify patients who might benefit from these drugs and to clarify the mechanisms of resistance to these compounds.

KEYWORDS:

• FGFR
• NSCLC
• FGFR TKI
• FGF

Article highlights

• Dysregulated FGFR signaling has a role in the development of several tumors including NSCLC.

• Amplification of FGFR1 are frequently observed in squamous NSCLC patients.

• FGFR inhibitors can be divided into two classes: selective FGFR TKIs, which include molecules directed against FGFR domain, and non-selective FGFR TKIs, which are multi target inhibitors.

• Currently several molecules targeting FGFR pathway are under investigation.

• Results of clinical trials investigating FGFR inhibitors, especially those on selective inhibitors, are disappointing.

This box summarizes key points contained in the article.

Declaration of interest

Simona Coco is a PhD supported by the Italian Ministry of Health (GR 2011-12, 02350922). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.