Abstract
The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to ‘(re)-educate’ TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.
Highlights
The tumor microenvironment (TME) can be defined as the complex and dynamic milieu where cancer cells are embedded
Given the relevance of cell metabolism in the TME, the purpose of the present review is to address how natural compounds shape the metabolism of key noncancer cells in the TME
The improved understanding of the central role of the TME in cancer development, progression, and response to treatment has opened a plethora of new perspectives on how modulating the complex tumor milieu, rather than targeting only malignant cells, could make a difference in therapeutic approaches
Summary
The tumor microenvironment (TME) can be defined as the complex and dynamic milieu where cancer cells are embedded. The enormous structural diversity, adequacy to chemical modification, and multitargeting activities of these compounds are some of the features that make them attractive as anticancer cytotoxic and/or cytostatic agents Many of these molecules have great potential to sensitize cancer cells to different therapeutic approaches, including radiotherapy, chemotherapy, and immunotherapy, as recently reviewed for flavonoids [10]. We will start by a brief description of TME cellular components and their metabolic plasticity, followed by illustrative examples of antitumoral metabolic reprogramming mediated by natural compounds This knowledge, combined with our understanding on the direct effects of these compounds in the metabolism of tumor cells (recently reviewed in [15,16]), is expected to provide a more integrated picture of the biological impact and therapeutic potential of these compounds as anticancer metabolic modulators
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