Stromal heterogeneity of tumor microenvironment (TME) plays a crucial role in malignancy and therapeutic resistance. Cancer-associated fibroblasts (CAFs) are one of the major players in tumor stroma. The heterogeneous sources of origin and subsequent impacts of crosstalk with breast cancer cells flaunt serious challenges before current therapies to cure triple-negative breast cancer (TNBC) and other cancers. The positive and reciprocal feedback of CAFs to induce cancer cells dictates their mutual synergy in establishing malignancy. Their substantial role in creating a tumor-promoting niche has reduced the efficacy of several anti-cancer treatments, including radiation, chemotherapy, immunotherapy, and endocrine therapy. Over the years, there has been an emphasis on understanding CAF-induced therapeutic resistance in order to enhance cancer therapy results. CAFs, in the majority of cases, employ crosstalk, stromal management, and other strategies to generate resilience in surrounding tumor cells. This emphasizes the significance of developing novel strategies that target particular tumor-promoting CAF subpopulations, which will improve treatment sensitivity and impede tumor growth. In this review, we discuss the current understanding of the origin and heterogeneity of CAFs, their role in tumor progression, and altering the tumor response to therapeutic agents in breast cancer. In addition, we also discuss the potential and possible approaches for CAF-mediated therapies.

Cancer is a current dreadful disease and the leading cause of death. Next to cardiovascular diseases, cancer is the most severe threat to human life and health. Breast cancer is the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed the biocompatible nanomaterials, CNTs-HAP and GR-HAP, through grafting of hydroxyapatite (HAP) to carbon nanotubes (CNTs) and graphene (GR) nanosheets. CNTs-HAP and GR-HAP have been tested for their cytotoxicity, growth and motility inhibitory effects, and their effects on the mesenchymal markers. All these demonstrated significant dose-dependent and time-dependent in vitro cytotoxicity against SUM-159 and MCF-7 breast cancer cell lines. The cell viability assay showed that the CNTs-HAP was more effective over SUM-159 cells than MCF-7 cells. It found that the increase in the concentration of GR-HAP has inhibited the clonogenic ability of breast cancer cells. The GR-HAP exhibited a substantial inhibitory effect on the cell motility of SUM-159 cell lines. It was investigated that the expression of vimentin (mesenchymal marker) was majorly reduced in SUM-159 cells by GR-HAP.