Engineering the Tumor Microenvironment: A novel strategy in Breast Cancer therapeutics

Abstract: Breast cancer is the most prevalent cancer and is leading cause of cancer related deaths among women worldwide. Increasing incidence and mortality for breast cancer, in spite of availability of various therapies, is a matter of deep concern. In the last few years, sufficient data has emerged to advocate role of various non-cancerous cells (stromal cells), present in the vicinity of cancer cells, in modulating proliferating/invasive properties of cancer cells. Proliferating tumor cells along with these non-cancerous cells comprises Tumor microenvironment (TME). Besides stromal cells, major immune cells infiltrate into TME and are linked to poor prognosis of breast cancer. Various molecules are secreted in the TME that impact proliferation, apoptotic behaviour, angiogenenic ability of cancer cell, along with extra-cellular matrix
remodeling. A significant cell population in breast TME is known to be tumor-associated macrophages (TAM), which is characterised by M2 phenotype, associated with pro-tumorogenic properties. TAMs are known to express various pro-angiogenic growth factors, cytokines, and chemokines and macrophage colony stimulating factor. Annexins, another class of molecules, have significant role in modulating TME and thus the disease state. Secretome studies have reported the presence of annexins A1-A6 in the secretome of the breast TME and their critical importance In light of the above studies, it is plausible that the components of TME can be crucial targets in defining invasive, anti-apoptotic and migratory behaviour of cancer cells. Targeting these molecules will be of great benefit for effective management of the disease.

Keywords: Annexins, cancer, macrophage polarization, tumor-associated macrophages, tumor microenvironment.