Abstract
Cancer-associated fibroblasts (CAF) are the most abundant cells of the tumor stroma and they critically influence cancer growth through control of the surrounding tumor microenvironment (TME). CAF-orchestrated reactive stroma, composed of pro-tumorigenic cytokines and growth factors, matrix components, neovessels, and deregulated immune cells, is associated with poor prognosis in multiple carcinomas, including breast cancer. Therefore, beyond cancer cells killing, researchers are currently focusing on TME as strategy to fight breast cancer. In recent years, nanomedicine has provided a number of smart delivery systems based on active targeting of breast CAF and immune-mediated overcome of chemoresistance. Many efforts have been made both to eradicate breast CAF and to reshape their identity and function. Nano-strategies for CAF targeting profoundly contribute to enhance chemosensitivity of breast tumors, enabling access of cytotoxic T-cells and reducing immunosuppressive signals. TME rearrangement also includes reorganization of the extracellular matrix to enhance permeability to chemotherapeutics, and nano-systems for smart coupling of chemo- and immune-therapy, by increasing immunogenicity and stimulating antitumor immunity. The present paper reviews the current state-of-the-art on nano-strategies to target breast CAF and TME. Finally, we consider and discuss future translational perspectives of proposed nano-strategies for clinical application in breast cancer.
Highlights
In recent years, the focus of cancer research has shifted from cancer to cancer-related stroma [1,2]
epithelial-to-mesenchymal transition (EMT) refers to the milieu of biological processes by which cancer cells gradually lose their epithelial hallmarks and acquire mesenchymal properties related to invasion of surrounding tissues and remodeling of the extracellular matrix (ECM) [6]
Which support tumor growth, generate a physical barrier against drugs and immune infiltration and facilitate cancer invasion [1,22,23,24,25]. This contributes to generate the drugs and immune infiltration and facilitate cancer invasion. This has contributes to generate so-called reactive stroma and to induce a desmoplastic reaction in tumor microenvironment (TME), which been associated with the prognosis so-called reactive stroma and to induce a desmoplastic reaction in TME, which has been poor in multiple carcinomas, including breast cancer [26,27,28]
Summary
The focus of cancer research has shifted from cancer to cancer-related stroma [1,2]. Tumor microenvironment (TME) plays a key role in several processes related to cancer progression, including the acquisition of an invasive phenotype, cell migration capability, chemoresistance, protection from antitumor immune response and neoangiogenesis [3]. EMT refers to the milieu of biological processes by which cancer cells gradually lose their epithelial hallmarks and acquire mesenchymal properties related to invasion of surrounding tissues and remodeling of the extracellular matrix (ECM) [6]. Abetween double-acting targeting both breast cancer cells strategy cancerincells. Nanomedicine could respond to this clinical unmet need, providing smart delivery clinical based unmeton need, providing smart systemsboth based on active systems active targeting and delivery internalization in cancer andtargeting in TME and cellsinternalization [12,13]. In the niche, ECM supports tumor regulates drug penetration.
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