Abstract

Breast cancer in the United States is the second most commonly diagnosed cancer in women. About 1 in 8 women will develop invasive breast cancer over the course of her lifetime and breast cancer remains the second leading cause of cancer-related death. In pursuit of novel therapeutic strategies, researchers have examined the tumor microenvironment as a potential anti-cancer target. In addition to neoplastic cells, the tumor microenvironment is composed of several critical normal cell types, including fibroblasts, vascular and lymph endothelial cells, osteoclasts, adipocytes, and immune cells. These cells have important roles in healthy tissue stasis, which frequently are altered in tumors. Indeed, tumor-associated stromal cells often contribute to tumorigenesis, tumor progression, and metastasis. Consequently, these host cells may serve as a possible target in anti-tumor and anti-metastatic therapeutic strategies. Targeting the tumor associated host cells offers the benefit that such cells do not mutate and develop resistance in response to treatment, a major cause of failure in cancer therapeutics targeting neoplastic cells. This review discusses the role of host cells in the tumor microenvironment during tumorigenesis, progression, and metastasis, and provides an overview of recent developments in targeting these cell populations to enhance cancer therapy efficacy.

Highlights

  • Breast cancer is the most frequently diagnosed cancer among women

  • The transition from ductal carcinoma in situ (DCIS) confined within the duct to invasive ductal carcinoma is a critical step in breast cancer progression that often leads to metastatic disease, which is associated with high mortality [6, 7]

  • While significant improvements in breast cancer managements have been made, treatment resistance and cancer cell dissemination limit the success of current therapeutic strategies

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Summary

Introduction

Breast cancer is the most frequently diagnosed cancer among women. It is estimated that in 2018, over 260,000 new cases will be diagnosed and over 40,000 deaths will be attributed to breast cancer in the United States alone [1]. Cells secrete PTH related peptide, which activates osteoclasts leading to the degradation of the bone matrix and the release of pro-tumorigenic growth factors [142, 151, 159].

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