scholarly journals Fundamentals of cancer metabolism

2016 ◽  
Vol 2 (5) ◽  
pp. e1600200 ◽  
Author(s):  
Ralph J. DeBerardinis ◽  
Navdeep S. Chandel
Keyword(s):  
Conceptual Framework ◽  
Tumor Cells ◽  
Recent Work ◽  
Cancer Metabolism ◽  
Human Cancer ◽  
Metabolic Reprogramming ◽  
Malignant Cells ◽  
Hallmarks Of Cancer ◽  
Altered Metabolism ◽  
New Strategies

Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer.

scholarly journals Metabolic Reprogramming in Breast Cancer and Its Therapeutic Implications

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 89 ◽  
Author(s):  
Nishant Gandhi ◽  
Gokul Das
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Cancer Metabolism ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Current Standard ◽  
Therapeutic Implications ◽  
Altered Metabolism

Current standard-of-care (SOC) therapy for breast cancer includes targeted therapies such as endocrine therapy for estrogen receptor-alpha (ERα) positive; anti-HER2 monoclonal antibodies for human epidermal growth factor receptor-2 (HER2)-enriched; and general chemotherapy for triple negative breast cancer (TNBC) subtypes. These therapies frequently fail due to acquired or inherent resistance. Altered metabolism has been recognized as one of the major mechanisms underlying therapeutic resistance. There are several cues that dictate metabolic reprogramming that also account for the tumors’ metabolic plasticity. For metabolic therapy to be efficacious there is a need to understand the metabolic underpinnings of the different subtypes of breast cancer as well as the role the SOC treatments play in targeting the metabolic phenotype. Understanding the mechanism will allow us to identify potential therapeutic vulnerabilities. There are some very interesting questions being tackled by researchers today as they pertain to altered metabolism in breast cancer. What are the metabolic differences between the different subtypes of breast cancer? Do cancer cells have a metabolic pathway preference based on the site and stage of metastasis? How do the cell-intrinsic and -extrinsic cues dictate the metabolic phenotype? How do the nucleus and mitochondria coordinately regulate metabolism? How does sensitivity or resistance to SOC affect metabolic reprogramming and vice-versa? This review addresses these issues along with the latest updates in the field of breast cancer metabolism.

scholarly journals Metabolic Reprogramming and Molecular Rewiring in Cancer: Therapeutic Opportunities

2021 ◽  
Vol 13 (2) ◽  
pp. 114-39
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Cancer Cells ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Term Survival ◽  
Metabolic Remodeling ◽  
New Strategy ◽  
Epigenetic Remodeling ◽  
Altered Metabolism

BACKGROUND: A lot of contemporary cancer research has concentrated on genetic influence. However, cancer also involves biochemical changes, such as metabolic adaptation to support the aberrant cell proliferation.CONTENT: The fast cell proliferation in cancer cells enforce a metabolic re-arrangement to promote their long-term survival. The increased glucose uptake and fermentation of glucose to lactate are common features of this altered metabolism known as “the Warburg effect”. These metabolic pathways regulation enable cancer cells to produce adenosine triphosphate (ATP) in an efficient way. Epigenetic and metabolic changes also both affect molecular rewiring in cancer cells and promote cancer development and progression.SUMMARY: Metabolic rewiring and epigenetic remodeling establishing a direct link between metabolism and nuclear transcription to promote the survival of tumor cells. A further understanding of how metabolic remodeling can result in epigenetic changes in tumors, affecting cancer cell differentiation, proliferation, and/or apoptosis, will lead to a new strategy for cancer therapy.KEYWORDS: cancer metabolism, epigenetics, metabolic reprogramming, molecular rewiring

scholarly journals Control of the Antitumor Immune Response by Cancer Metabolism

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 104 ◽  
Author(s):  
Charlotte Domblides ◽  
Lydia Lartigue ◽  
Benjamin Faustin
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Cancer Metabolism ◽  
Hematological Malignancies ◽  
Immune Cell ◽  
Immune Escape ◽  
Positive Impact ◽  
Metabolic Reprogramming ◽  
Antitumor Immune Response ◽  
Molecular Events

The metabolic reprogramming of tumor cells and immune escape are two major hallmarks of cancer cells. The metabolic changes that occur during tumorigenesis, enabling survival and proliferation, are described for both solid and hematological malignancies. Concurrently, tumor cells have deployed mechanisms to escape immune cell recognition and destruction. Additionally, therapeutic blocking of tumor-mediated immunosuppression has proven to have an unprecedented positive impact in clinical oncology. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune signaling through both the release of signaling molecules and the expression of immune membrane ligands. Here, we review these molecular events to highlight the contribution of cancer cell metabolic reprogramming on the shaping of the antitumor immune response.

scholarly journals Linking Metabolic Reprogramming, Plasticity and Tumor Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 762
Author(s):  
Oleg Shuvalov ◽  
Alexandra Daks ◽  
Olga Fedorova ◽  
Alexey Petukhov ◽  
Nickolai Barlev
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Anticancer Therapy ◽  
Metabolic Reprogramming ◽  
Hallmarks Of Cancer ◽  
Primary Tumors ◽  
Molecular Features ◽  
Altered Metabolism ◽  
Key Features ◽  
Tissue Of Origin

The specific molecular features of cancer cells that distinguish them from the normal ones are denoted as “hallmarks of cancer”. One of the critical hallmarks of cancer is an altered metabolism which provides tumor cells with energy and structural resources necessary for rapid proliferation. The key feature of a cancer-reprogrammed metabolism is its plasticity, allowing cancer cells to better adapt to various conditions and to oppose different therapies. Furthermore, the alterations of metabolic pathways in malignant cells are heterogeneous and are defined by several factors including the tissue of origin, driving mutations, and microenvironment. In the present review, we discuss the key features of metabolic reprogramming and plasticity associated with different stages of tumor, from primary tumors to metastases. We also provide evidence of the successful usage of metabolic drugs in anticancer therapy. Finally, we highlight new promising targets for the development of new metabolic drugs.

scholarly journals Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3318
Author(s):  
Marina Serra ◽  
Amedeo Columbano ◽  
Andrea Perra ◽  
Marta Anna Kowalik
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Metabolic Profile ◽  
Cancer Metabolism ◽  
Therapeutic Strategies ◽  
Metabolic Changes ◽  
Metabolic Reprogramming ◽  
Rodent Models ◽  
Hallmarks Of Cancer ◽  
The Core

Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC.

scholarly journals Interplay between Metabolism Reprogramming and Epithelial-to-Mesenchymal Transition in Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1973
Author(s):  
Yoann Daniel ◽  
Elise Lelou ◽  
Caroline Aninat ◽  
Anne Corlu ◽  
Florian Cabillic
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Energy Needs ◽  
New Strategies ◽  
Pro Inflammatory Cytokines

Tumor cells display important plasticity potential, which contributes to intratumoral heterogeneity. Notably, tumor cells have the ability to retrodifferentiate toward immature states under the influence of their microenvironment. Importantly, this phenotypical conversion is paralleled by a metabolic rewiring, and according to the metabostemness theory, metabolic reprogramming represents the first step of epithelial-to-mesenchymal transition (EMT) and acquisition of stemness features. Most cancer stem cells (CSC) adopt a glycolytic phenotype even though cells retain functional mitochondria. Such adaptation is suggested to reduce the production of reactive oxygen species (ROS), protecting CSC from detrimental effects of ROS. CSC may also rely on glutaminolysis or fatty acid metabolism to sustain their energy needs. Besides pro-inflammatory cytokines that are well-known to initiate the retrodifferentiation process, the release of catecholamines in the microenvironment of the tumor can modulate both EMT and metabolic changes in cancer cells through the activation of EMT transcription factors (ZEB1, Snail, or Slug (SNAI2)). Importantly, the acquisition of stem cell properties favors the resistance to standard care chemotherapies. Hence, a better understanding of this process could pave the way for the development of therapies targeting CSC metabolism, providing new strategies to eradicate the whole tumor mass in cancers with unmet needs.

scholarly journals Cancer metabolism and intervention therapy

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Yongsheng Li
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Proliferation And Metastasis ◽  
Immunosuppressive Microenvironment

AbstractMetabolic reprogramming with heterogeneity is a hallmark of cancer and is at the basis of malignant behaviors. It supports the proliferation and metastasis of tumor cells according to the low nutrition and hypoxic microenvironment. Tumor cells frantically grab energy sources (such as glucose, fatty acids, and glutamine) from different pathways to produce a variety of biomass to meet their material needs via enhanced synthetic pathways, including aerobic glycolysis, glutaminolysis, fatty acid synthesis (FAS), and pentose phosphate pathway (PPP). To survive from stress conditions (e.g., metastasis, irradiation, or chemotherapy), tumor cells have to reprogram their metabolism from biomass production towards the generation of abundant adenosine triphosphate (ATP) and antioxidants. In addition, cancer cells remodel the microenvironment through metabolites, promoting an immunosuppressive microenvironment. Herein, we discuss how the metabolism is reprogrammed in cancer cells and how the tumor microenvironment is educated via the metabolic products. We also highlight potential metabolic targets for cancer therapies.

scholarly journals Mucin1 and Mucin16: Therapeutic Targets for Cancer Therapy

2021 ◽  
Vol 14 (10) ◽  
pp. 1053
Author(s):  
Dong-Hee Lee ◽  
Seunghyun Choi ◽  
Yoon Park ◽  
Hyung-seung Jin
Keyword(s):  
Cell Growth ◽  
Cancer Therapy ◽  
Immune Evasion ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Structural Features ◽  
Metabolic Reprogramming ◽  
Cancer Development ◽  
Hallmarks Of Cancer ◽  
Mucus Barrier

The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.

scholarly journals Metabolic Reprogramming of Triple-Negative Breast Cancer: The Role of miRNAs

2017 ◽  
Vol 3 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Amal Qattan
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Metabolism ◽  
Current Knowledge ◽  
Human Cancer ◽  
Tricarboxylic Acid Cycle ◽  
Locally Advanced ◽  
Mrna Translation ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype

AbstractMicroRNAs (miRNAs) are well known to influence the expression of the genes that regulate critical cellular functions. Various reports have suggested that they play critical roles in breast cancer metabolism through the regulation of various metabolic pathways, including the metabolism of glucose, lipids, glycolysis and the mitochondrial tricarboxylic acid cycle (TCA). miRNAs regulate the metabolic process by targeting key molecules (enzymes, kinases transporters) or by modifying the expression of key transcription molecules. In addition, miRNAs can indirectly regulate mRNA translation by targeting chromatin-remodeling enzymes. Furthermore, miRNAs influence the expression of both oncogenes and tumor suppressors and have a major impact on PI3K/AKT, HIF, and MYC signal transduction, which contributes to the metabolic phenotype in human cancer. Although human epidermal growth factor and endocrine therapies have been effective in treating breast cancer, for locally advanced and distant metastases mortality remains high. Drug resistance and recurrence remain major hurdles for advanced breast cancer therapy. Given the critical influence of metabolic reprogramming in the progression of neoplasm, tumorigenesis and metastasis, research should focus on novel targets of metabolic enzymes to reverse drug resistance and improve overall survival rates. Blocking the miRNAs that contribute to metabolic reprogramming or the use of exogenous miRNAs as antisense oligonucleotides, may be an effective way to treat aggressive, chemo-resistant cancers. This review summarizes current knowledge on the mechanism of action of miRNAs in altering the metabolism of cancer cells and presents possible therapeutic approaches to treating breast cancers that are resistant to current drugs.

scholarly journals TRIM21 and PHLDA3 Negatively Regulate the Cross-Talk between the PI3K/AKT Pathway and PPP Metabolism

2019 ◽  
Author(s):  
Jie Cheng ◽  
Yan Huang ◽  
Xiaohui Zhang ◽  
Yue Yu ◽  
Wanru Zhang ◽  
...  
Keyword(s):  
Reciprocal Cross ◽  
Cancer Metabolism ◽  
Human Cancer ◽  
Therapeutic Benefit ◽  
Metabolic Reprogramming ◽  
Akt Pathway ◽  
Akt Inhibitor ◽  
Akt Activation ◽  
The Cross

SUMMARYPI3K/AKT signaling is known to regulate cancer metabolism but whether metabolic pathway feedbacks and regulates the PI3K/AKT pathway is unclear. Here, we demonstrate the important reciprocal cross-talks between the PI3K/AKT signal and PPP branching metabolic pathways. PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of PPP, by inhibiting a newly identified E3 ligase TIRM21, and promotes PPP. PPP metabolites, in turn, reinforce AKT activation and further promote cancer metabolic reprogramming by blocking the expression of an AKT inhibitor PHLDA3. Knockout TRIM21 or PHLDA3 promotes the cross-talks and cell proliferation. Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of these reciprocal cross-talks may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.

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