Oncometabolites—A Link between Cancer Cells and Tumor Microenvironment

SIMPLE SUMMARY: Lactate, glutamate, fumarate, and succinate are metabolites that accumulate in tumors as a consequence of an alteration in cellular respiration connected with malignant transformation. These metabolites link all types of cells involved in tumor survival and progression, so they are also called oncometabolites. Here, we describe the pathways that lead to the accumulation of lactate, glutamate, fumarate, and succinate in solid tumors and their impact on shaping the tumor microenvironment. The data show that oncometabolites play a particularly important role in neoangiogenesis and in the regulation of the immune component of tumor. Oncometabolites are also associated with a disrupted DNA damage response and make the tumor microenvironment more favorable for cell migration. The knowledge summarized in this article will allow for a better understanding of the associations between cancer cells and the tumor microenvironment as well as the direct effects of these particles on cancer development. ABSTRACT: The tumor microenvironment is the space between healthy tissues and cancer cells, created by the extracellular matrix, blood vessels, infiltrating cells such as immune cells, and cancer-associated fibroblasts. These components constantly interact and influence each other, enabling cancer cells to survive and develop in the host organism. Accumulated intermediate metabolites favoring dysregulation and compensatory responses in the cell, called oncometabolites, provide a method of communication between cells and might also play a role in cancer growth. Here, we describe the changes in metabolic pathways that lead to accumulation of intermediate metabolites: lactate, glutamate, fumarate, and succinate in the tumor and their impact on the tumor microenvironment. These oncometabolites are not only waste products, but also link all types of cells involved in tumor survival and progression. Oncometabolites play a particularly important role in neoangiogenesis and in the infiltration of immune cells in cancer. Oncometabolites are also associated with a disrupted DNA damage response and make the tumor microenvironment more favorable for cell migration. The knowledge summarized in this article will allow for a better understanding of associations between therapeutic targets and oncometabolites, as well as the direct effects of these particles on the formation of the tumor microenvironment. In the future, targeting oncometabolites could improve treatment standards or represent a novel method for fighting cancer.