Tumor Microenvironment and Metabolism

Abstract

The tumor microenvironment has profound effects on cancer development, progression, and therapeutic response. Cancer cells co-exist with infiltrated immune cells, blood vessels, fibroblasts, and other stromal cells in the tumor microenvironment [1]. Deviated from their normal physiological roles, immune, vascular, and stromal cells in a tumor are often dysfunctional and exploited by cancer cells to promote tumor progression. Additionally, biochemical and biophysical characteristics of the tumor microenvironment are distinct from that in normal tissues. Several hallmarks of the tumor microenvironment, including hypoxia, acidosis, high interstitial fluid pressure, and increased extracellular matrix (ECM) stiffness, have been identified [2–7]. As initially proposed in the “seed and soil” hypothesis by Stephen Paget more than a century ago, tissue microenvironment is critical for cancer metastasis [8,9]. It has also been demonstrated that microenvironmental factors play important roles in multiple stages of cancer progression and in the modulation of cancer therapeutic responses [2–7]. Therapeutics targeting crucial components of the tumor microenvironment, such as blood vessels and immune cells, have been added to the arsenals of cancer therapy [1,3,10].