Cancer associated fibroblasts: role in breast cancer and potential as therapeutic targets

ABSTRACT

Introduction: Cancer associated fibroblasts (CAFs) are the largest population of stromal cells in breast tumors. Emerging evidence has suggested that CAFs are important players not only in fostering tumor growth and spread but also in altering the tumor response to therapeutic agents. On the basis of these observations, huge efforts have been made to exploit CAFs as potential targets for breast cancer therapy.

Areas covered: The current understanding of the hallmarks and biology of CAFs, their multilayered interplay with various cell populations of breast tumor microenvironment toward cancer initiation, progression, metastasis and resistance to anticancer therapies are discussed. In addition, a comprehensive overview of the CAFs-based molecular druggable targets in breast tumors is provided. The most relevant literature, in particular the studies retrieved in Medline in the last 10 years, served for this purpose.

Expert opinion: The interest on CAFs as a target to fight breast cancer has becoming a hot topic for drug discovery. Indeed, several CAFs-targeted approaches are emerging as appealing therapeutic strategies in breast cancer. At pre-clinical level, this research field is speedily advancing toward the assessment of successful tactics targeting CAFs in breast cancer. Therefore, anti-CAFs therapies may display an intriguing potential to be exploited in clinical studies.

KEYWORDS:

• Cancer Associated Fibroblasts (CAFs)
• breast tumor microenvironment
• breast cancer
• targeted therapy
• molecular targets
• oncogenic signaling

Article Highlights

1. Cancer-Associated Fibroblasts (CAFs) are the most abundant non tumor-population in the breast cancer microenvironment.

2. CAFs serve as facilitator of multiple molecular interactions between breast cancer cells and the surrounding stroma.

3. Molecular interactions mediated by CAFs are involved in the acquisition of malignant features in breast cancer.

4. A better understanding of CAFs-mediated action would unveil novel molecular targets in therapeutic settings.

5. Pre-clinical models have shown the role elicited by CAFs in breast cancer, CAFs may therefore be regarded as a promising platform in clinical studies.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Declaration of interest

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

Fondazione AIRC supported A Belfiore (IG n. 23369), MM (IG n. 21322) and EMDF (Start-Up Grant 21651). DC Rigiracciolo was supported by Italian Minister of University and Research[MIUR, D.D. n. 3407/2018]-PON R&I 2014-2020 ‘AIM Attrazione e Mobilità Internazionale’. R Lappano, DC Rigiracciolo and M Maggiolini acknowledge i) the special award namely ‘Department of Excellence 2018-2022’ (Italian Law 232/2016) to the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (Italy), ii) the ‘Sistema Integrato di Laboratori per L’Ambiente – (SILA) PONa3_00341’.