FGFR-targeted therapeutics for the treatment of breast cancer

ABSTRACT

Introduction: Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients.

Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed.

Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

KEYWORDS:

• Fibroblast growth factor receptor
• FGFR genetic alterations
• breast cancer
• FGFR-targeted agents

Article highlights

• Deregulated FGFR signaling has been described in breast cancer.

• Various classes of FGFR inhibitors are in clinical development in different tumor types, including breast cancer. Small molecules FGFR TKIs are the agents in the more advanced phase of clinical development.

• Different clinical trials are ongoing in FGFR-aberrant breast cancer.

• Further investigations on the role of FGFR aberrations, on the selection of patients that might benefit of FGFR inhibitors and on the opportunity of using combinations with targeted-based agents will help to improve the efficacy of anti-FGFR therapies in breast cancer.

This box summarizes key points contained in the article.

Acknowledgments

We thank Alessandra Trocino (INT ‘Fondazione G. Pascale’, Naples, Italy) for bibliographic assistance.

Declaration of interest

N. Normanno was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC) (Grant number: IG17135). The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was not funded.