Challenges of targeting tumor microenvironment in prostate cancer

Abstract

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in American men. PCa patients often die of the aggressive forms of the malignancy at advanced stages such as distant metastasis. There are urgent need to understand the molecular mechanisms driving PCa progression and subsequently develop efficient therapeutics to improve men’s health in the US as well as the world. Tumor microenvironment (TME) has been realized to play a critical role in PCa progression and metastasis, and targeting key factors of the TME has become the logical strategy for efficiently controlling PCa malignancy. Stromal cells in prostate tumors secrete growth factors, cytokines, and extracellular matrix (ECM) proteins that provide the TME to fuel cell proliferation, invasion, and metastasis. This review will focus on several key factors influencing TME, which include cancer-associated fibroblasts (CAFs), ECM remodeling, androgen receptor (AR) signaling, inflammation, and hypoxia. We will explain and analyze the biological roles of these factors and their important contributions to PCa malignancy, targeted therapeutics, and drug resistance. Furthermore, we will discuss the contributions of the dysregulation of epigenetic regulators to the complexity of the TME in PCa.