Chapter 3 - Autotaxin is an important component of the tumor microenvironment and a major modulator of therapy responses for breast cancer

Abstract

Due to improved targeted therapies and early diagnosis, the 5–10year survival rates for breast cancer patients has greatly improved. However, de novo therapy resistance and metastatic breast cancer tumors remain a major clinical challenge in long-term management of the disease. Recent evidence now indicates that the tumor microenvironment (TME) exerts profound influence on the success of chemotherapies and radiotherapy by modulating cell survival, proliferation, and tumor heterogeneity. As the major nonmalignant cellular components of TME in breast cancer, adipocytes, fibroblasts, leukocytes, and vascular endothelial cells through cell-cell contact and secreted factors (e.g., autotaxin) support cancer cell survival and proliferation and decrease drug efficacy. The noncellular components of TME such as extracellular proteins also play essential roles in providing alternative cell survival mechanisms, offering additional protection against anticancer therapeutics. The development of 3-dimensional organoid cultures has now made it possible to recreate the tumor microenvironment using primary breast tumors and to separately examine the role of cellular and noncellular components of the TME on therapy responses. Some interesting data have emerged and in this review article, we will discuss autotaxin as a major enzyme secreted by the adipocytes and stromal cells of TME and how it impacts therapy response and tumor progression. Moreover, we examine recent experimental approaches to study TME mechanisms that impact therapy response in breast cancer tumors.