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Effects of metabolic cancer therapy on tumor microenvironment
Petra Hyroššová1, Mirko Milošević1,2, Josef Škoda1
1Institute of Biotechnology of the Czech Academy of Sciences, Prague, Czechia.
Abstract:
Targeting tumor metabolism for cancer therapy is an old strategy. In fact, historically the first effective cancer therapeutics were directed at nucleotide metabolism. The spectrum of metabolic drugs considered in cancer increases rapidly - clinical trials are in progress for agents directed at glycolysis, oxidative phosphorylation, glutaminolysis and several others. These pathways are essential for cancer cell proliferation and redox homeostasis, but are also required, to various degrees, in other cell types present in the tumor microenvironment, including immune cells, endothelial cells and fibroblasts. How metabolism-targeted treatments impact these tumor-associated cell types is not fully understood, even though their response may co-determine the overall effectivity of therapy. Indeed, the metabolic dependencies of stromal cells have been overlooked for a long time. Therefore, it is important that metabolic therapy is considered in the context of tumor microenvironment, as understanding the metabolic vulnerabilities of both cancer and stromal cells can guide new treatment concepts and help better understand treatment resistance. In this review we discuss recent findings covering the impact of metabolic interventions on cellular components of the tumor microenvironment and their implications for metabolic cancer therapy.
Insights
Targeting cancer cell metabolism is a key strategy. This review explores how metabolic therapies affect the tumor microenvironment, including stromal cells, to improve cancer treatment effectiveness.
Area of Science:
- Oncology
- Cancer Metabolism
- Tumor Microenvironment
Background:
- Cancer therapy has historically targeted nucleotide metabolism.
- Metabolic drug development for cancer is rapidly expanding, with agents targeting glycolysis, oxidative phosphorylation, and glutaminolysis in clinical trials.
- These metabolic pathways are crucial for cancer cell proliferation and redox balance, but also support other cells within the tumor microenvironment.
Purpose of the Study:
- To review recent findings on the impact of metabolic interventions on tumor microenvironment cellular components.
- To highlight the implications of these impacts for metabolic cancer therapy.
- To emphasize the importance of considering the tumor microenvironment in metabolic therapy strategies.
Main Methods:
- Literature review of recent research findings.
- Analysis of the effects of metabolic interventions on various cell types within the tumor microenvironment.
- Discussion of the implications for cancer treatment strategies.
Main Results:
- Metabolic interventions impact not only cancer cells but also immune cells, endothelial cells, and fibroblasts within the tumor microenvironment.
- The metabolic dependencies of stromal cells have been largely overlooked.
- Understanding these interactions is crucial for effective cancer therapy.
Conclusions:
- Metabolic therapy must be considered within the broader context of the tumor microenvironment.
- Identifying metabolic vulnerabilities in both cancer and stromal cells can lead to novel treatment concepts.
- This knowledge can also improve the understanding of treatment resistance mechanisms in cancer.
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