Abstract:Metabolic transformation is a hallmark of cancer and a critical target for cancer therapy. Cancer metabolism and behavior are regulated by cell-intrinsic factors, as well as metabolite availability in the tumor microenvironment (TME). This metabolic niche within the TME is shaped by four tiers of regulation, including: 1) intrinsic tumor cell metabolism, 2) interactions between cancer and non-cancerous cells, 3) tumor location and heterogeneity, and 4) whole-body metabolic homeostasis. Here, we will define the… Show more
“…In addition to metabolic alterations that are intrinsic to cancer cells, it is also increasingly recognized that metabolic alterations occur in other cells within the tumor microenvironment; these changes can also contribute to cancer progression (reviewed by Elia and Haigis 79 and Lyssiotis and Kimmelman 80 ). Furthermore, cancer cell heterogeneity and plasticity can also manifest as metabolic heterogeneity.…”
Section: Metabolism In Tumors and Patients With Cancermentioning
confidence: 99%
“…Furthermore, both intrinsic factors (genomic/epigenomic alterations) and extrinsic factors (nutrients, drugs, hormones, and interactions with stromal cells, extracellular matrix, and the immune system) contribute to the metabolic reprogramming of cancer cells. For further information, the reader is referred to recent reviews of these topics 2,79,96 …”
Section: Metabolism In Tumors and Patients With Cancermentioning
Cancer has myriad effects on metabolism that include both rewiring of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment, and changes in normal tissue metabolism. With the recognition that fluorodeoxyglucose-positron emission tomography imaging is an important tool for the management of many cancers, other metabolites in biological samples have been in the spotlight for cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecule metabolites that like other -omics technologies can provide critical information about the cancer state that are otherwise not apparent. Here, the authors review how cancer and cancer therapies interact with metabolism at the cellular and systemic levels. An overview of metabolomics is provided with a focus on currently available technologies and how they have been applied in the clinical and translational research setting. The authors also discuss how metabolomics could be further leveraged in the future to improve the management of patients with cancer.
“…In addition to metabolic alterations that are intrinsic to cancer cells, it is also increasingly recognized that metabolic alterations occur in other cells within the tumor microenvironment; these changes can also contribute to cancer progression (reviewed by Elia and Haigis 79 and Lyssiotis and Kimmelman 80 ). Furthermore, cancer cell heterogeneity and plasticity can also manifest as metabolic heterogeneity.…”
Section: Metabolism In Tumors and Patients With Cancermentioning
confidence: 99%
“…Furthermore, both intrinsic factors (genomic/epigenomic alterations) and extrinsic factors (nutrients, drugs, hormones, and interactions with stromal cells, extracellular matrix, and the immune system) contribute to the metabolic reprogramming of cancer cells. For further information, the reader is referred to recent reviews of these topics 2,79,96 …”
Section: Metabolism In Tumors and Patients With Cancermentioning
Cancer has myriad effects on metabolism that include both rewiring of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment, and changes in normal tissue metabolism. With the recognition that fluorodeoxyglucose-positron emission tomography imaging is an important tool for the management of many cancers, other metabolites in biological samples have been in the spotlight for cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecule metabolites that like other -omics technologies can provide critical information about the cancer state that are otherwise not apparent. Here, the authors review how cancer and cancer therapies interact with metabolism at the cellular and systemic levels. An overview of metabolomics is provided with a focus on currently available technologies and how they have been applied in the clinical and translational research setting. The authors also discuss how metabolomics could be further leveraged in the future to improve the management of patients with cancer.
“… 95–97 In addition, metformin restricts calorie intake, which reduces lipid uptake by cancer cells from plasma and tissue fluid, increases toxic saturated fatty acid levels by inhibiting the activity of stearoyl coenzyme A desaturase, and inhibits the progression of pancreatic ductal adenocarcinoma. 98 Figure 2 Metformin inhibits cancer by suppressing lipid metabolism. …”
Section: The Possible Antitumor Mechanism Of Metforminmentioning
Malignant tumors are a major cause of death, and their incidence is increasing worldwide. Although the survival rate for some cancers has improved, treatments for other malignant tumors are limited, and their mortality rate continues to increase. People with type 2 diabetes have a higher risk of malignant tumors and a higher mortality rate than those without diabetes. Metformin is a commonly used hypoglycemic drug. In recent years, a growing number of studies have indicated that metformin has antitumor effects and increases the sensitivity of malignant tumors to chemotherapy. However, the effect of metformin on different tumors is currently controversial, and the mechanism of metformin’s antitumor action is not fully understood. Insights into the effect of metformin on malignant tumors and the possible mechanism may contribute to the development of antitumor drugs.
“…Metabolism and thus tumor behavior are regulated by metabolite availability in the tumor microenvironment [ 159 ]. As a metabolic niche, the tumor microenvironment is shaped by intrinsic tumor cell metabolism, interactions between tumor and non-tumor cells, and systemic metabolism [ 2 , 160 ]. The metabolic modification produced by lactate accumulation in the extracellular matrix acts as a resistance mechanism related to OXPHOS mitochondrial dysfunction.…”
Section: Intervention Opportunities From a Metabolic View Of Cancermentioning
confidence: 99%
“…Metabolic alterations in tumor cells to provide increased energy function, known as metabolic reprogramming, facilitate proliferation, infiltrative capacity, distant growth, and treatment resistance, among other tumor activities. This is a crucial hallmark of tumorigenesis, underpinning the specific alterations of each tumor change, regardless of the biological perspective (morphological, biochemical, physical, immunophenotypic, molecular or genetic) adopted [ 1 , 2 ]. The metabolic profile of the tumor determines the biological properties of tumor cells, immune response, tumor microenvironment configuration, morphological and molecular tumor heterogeneity, and many other variables, including treatment response and prognosis [ 3 , 4 ].…”
A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.
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