Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Abstract

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

Engineering hyaluronic acid-based cryogels for CD44-mediated breast tumor reconstruction

“…Lastly, it has been reported that cancer-associated fibroblasts contribute to therapy resistance and metastasis, and endothelial cells play an active role in promoting breast cancer proliferation [ 97 ]. With that in mind, HAGM cryogels could be used for MCTS co-cultures of breast cancer cells, fibroblasts, and endothelial cells to better model breast tumor heterogeneity and complexity [ 98 , 99 ].…”

High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients

“…These findings indicate that the expression level of AUF1 in breast CAFs has a powerful prognostic value for TNBC as well as ER+/Her2− patients. In fact, several lines of evidence point to the key role of CAFs in modulating the response of breast cancer patients to various types of therapies [ 20 ].…”

Pan-Cancer Analysis Reveals the Relation between TRMT112 and Tumor Microenvironment

“…The TME exerts crucial roles in tumor proliferation, invasion, metastasis, angiogenesis, metabolism, immunosuppression, and drug resistance [ 28 , 29 ]. Being the most important mesenchymal component in the TME, tumor-associated fibroblasts contribute to the pathogenesis of tumors by releasing diverse growth factors, chemokines, and cytokines and participating in the remodeling of the extracellular matrix [ 30 – 33 ]. Here, TRMT112 expression was discovered to exhibit a positive link to tumor-associated fibroblasts in BRCA, ESCA, UCEC, and COAD.…”