-
Cancer Metastasis Reviews Mar 2024Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic... (Review)
Review
Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.
Topics: Humans; Lipid Metabolism; Cell Plasticity; Neoplasms; Drug Resistance, Neoplasm; Cholesterol
PubMed: 38438800
DOI: 10.1007/s10555-024-10170-1 -
Endocrinology and Metabolism (Seoul,... Jun 2024Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and... (Review)
Review
Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and have a higher risk of mortality. Inhibiting RET and BRAF kinases has emerged as a potential therapeutic strategy for the treatment of thyroid cancer, particularly in cases of advanced or aggressive disease. However, the development of resistance mechanisms may limit the efficacy of these kinase inhibitors. Therefore, developing precise strategies to target thyroid cancer cell metabolism and overcome resistance is a critical area of research for advancing thyroid cancer treatment. In the field of cancer therapeutics, researchers have explored combinatorial strategies involving dual metabolic inhibition and metabolic inhibitors in combination with targeted therapy, chemotherapy, and immunotherapy to overcome the challenge of metabolic plasticity. This review highlights the need for new therapeutic approaches for thyroid cancer and discusses promising metabolic inhibitors targeting thyroid cancer. It also discusses the challenges posed by metabolic plasticity in the development of effective strategies for targeting cancer cell metabolism and explores the potential advantages of combined metabolic targeting.
Topics: Humans; Thyroid Neoplasms; Protein Kinase Inhibitors; Cellular Reprogramming; Molecular Targeted Therapy; Metabolic Reprogramming
PubMed: 38853437
DOI: 10.3803/EnM.2023.1802 -
Reviews in Medical Virology Jan 2024Viruses change the host cell metabolism to produce infectious particles and create optimal conditions for replication and reproduction. Numerous host cell pathways have... (Review)
Review
Viruses change the host cell metabolism to produce infectious particles and create optimal conditions for replication and reproduction. Numerous host cell pathways have been modified to ensure available biomolecules and sufficient energy. Metabolomics studies conducted over the past decade have revealed that eukaryotic viruses alter the metabolism of their host cells on a large scale. Modifying pathways like glycolysis, fatty acid synthesis and glutaminolysis could provide potential energy for virus multiplication. Thus, almost every virus has a unique metabolic signature and a different relationship between the viral life cycle and the individual metabolic processes. There are enormous research in virus induced metabolic reprogramming of host cells that is being conducted through numerous approaches using different vaccine candidates and antiviral drug substances. This review provides an overview of viral interference to different metabolic pathways and improved monitoring in this area will open up new ways for more effective antiviral therapies and combating virus induced oncogenesis.
Topics: Humans; Viruses; Metabolic Networks and Pathways; Glycolysis; Virus Replication
PubMed: 38282396
DOI: 10.1002/rmv.2505 -
Antioxidants & Redox Signaling Jul 2023Protein persulfidation (the formation of RSSH), an evolutionarily conserved oxidative posttranslational modification in which thiol groups in cysteine residues are... (Review)
Review
Protein persulfidation (the formation of RSSH), an evolutionarily conserved oxidative posttranslational modification in which thiol groups in cysteine residues are converted into persulfides, has emerged as one of the main mechanisms through which hydrogen sulfide (HS) conveys its signaling. New methodological advances in persulfide labeling started unraveling the chemical biology of this modification and its role in (patho)physiology. Some of the key metabolic enzymes are regulated by persulfidation. RSSH levels are important for the cellular defense against oxidative injury, and they decrease with aging, leaving proteins vulnerable to oxidative damage. Persulfidation is dysregulated in many diseases. A relatively new field of signaling by protein persulfidation still has many unanswered questions: the mechanism(s) of persulfide formation and transpersulfidation and the identification of "protein persulfidases," the improvement of methods to monitor RSSH changes and identify protein targets, and understanding the mechanisms through which this modification controls important (patho)physiological functions. Deep mechanistic studies using more selective and sensitive RSSH labeling techniques will provide high-resolution structural, functional, quantitative, and spatiotemporal information on RSSH dynamics and help with better understanding how HS-derived protein persulfidation affects protein structure and function in health and disease. This knowledge could pave the way for targeted drug design for a wide variety of pathologies. 39, 19-39.
Topics: Sulfides; Hydrogen Sulfide; Signal Transduction; Oxidative Stress; Oxidation-Reduction; Biology
PubMed: 37288744
DOI: 10.1089/ars.2023.0352 -
International Journal of Molecular... Dec 2023Sphingolipids are involved in cell signaling and metabolic pathways, and their metabolites play a critical role in host defense against intracellular pathogens. Here, we... (Review)
Review
Sphingolipids are involved in cell signaling and metabolic pathways, and their metabolites play a critical role in host defense against intracellular pathogens. Here, we review the known mechanisms of sphingolipids in viral infections and discuss the potential implication of the study of sphingolipid metabolism in vaccine and therapeutic development.
Topics: Humans; Sphingolipids; Virus Diseases; Signal Transduction; Lipid Metabolism; Metabolic Networks and Pathways; Sphingosine
PubMed: 38139132
DOI: 10.3390/ijms242417303 -
Biomedicine & Pharmacotherapy =... Dec 2023Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, presents severe threats to women's health. Therefore, it is critical to find novel... (Review)
Review
Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, presents severe threats to women's health. Therefore, it is critical to find novel treatment approaches. Ferroptosis, a newly identified form of programmed cell death, is marked by the buildup of lipid reactive oxygen species (ROS) and high iron concentrations. According to previous studies, ferroptosis sensitivity can be controlled by a number of metabolic events in cells, such as amino acid metabolism, iron metabolism, and lipid metabolism. Given that TNBC tumors are rich in iron and lipids, inducing ferroptosis in these tumors is a potential approach for TNBC treatment. Notably, the metabolic adaptability of cancer cells allows them to coordinate an attack on one or more metabolic pathways to initiate ferroptosis, offering a novel perspective to improve the high drug resistance and clinical therapy of TNBC. However, a clear picture of ferroptosis in TNBC still needs to be completely revealed. In this review, we provide an overview of recent advancements regarding the connection between ferroptosis and amino acid, iron, and lipid metabolism in TNBC. We also discuss the probable significance of ferroptosis as an innovative target for chemotherapy, radiotherapy, immunotherapy, nanotherapy and natural product therapy in TNBC, highlighting its therapeutic potential and application prospects.
Topics: Female; Humans; Triple Negative Breast Neoplasms; Ferroptosis; Lipid Metabolism; Amino Acids; Iron; Cell Line, Tumor
PubMed: 37951026
DOI: 10.1016/j.biopha.2023.115866 -
Clinical and Translational Medicine Jan 2024One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic... (Review)
Review
BACKGROUND
One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients.
METHODS
We collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy.
RESULTS
In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future.
CONCLUSION
Targeting one-carbon metabolism is useful for cancer immunotherapy.
Topics: Humans; Neoplasms; Antineoplastic Agents; Metabolic Networks and Pathways; Carbon
PubMed: 38279895
DOI: 10.1002/ctm2.1521 -
Clinical and Translational Medicine Nov 2023The study and synthesis of membrane organelles are becoming increasingly important, not only as simplified cellular models for corresponding molecular and metabolic... (Review)
Review
BACKGROUND
The study and synthesis of membrane organelles are becoming increasingly important, not only as simplified cellular models for corresponding molecular and metabolic studies but also for applications in synthetic biology of artificial cells and drug delivery vehicles. Lipid droplets (LDs) are central organelles in cellular lipid metabolism and are involved in almost all metabolic processes. Multiple studies have also demonstrated a high correlation between LDs and metabolic diseases. During these processes, LDs reveal a highly dynamic character, with their lipid fraction, protein composition and subcellular localisation constantly changing in response to metabolic demands. However, the molecular mechanisms underlying these functions have not been fully understood due to the limitations of cell biology approaches. Fortunately, developments in synthetic biology have provided a huge breakthrough for metabolism research, and methods for in vitro synthesis of LDs have been successfully established, with great advances in protein binding, lipid function, membrane dynamics and enzymatic reactions.
AIMS AND METHODS
In this review, we provide a comprehensive overview of the assembly and function of endogenous LDs, from the generation of lipid molecules to how they are assembled into LDs in the endoplasmic reticulum. In particular, we highlight two major classes of synthetic LD models for fabrication techniques and their recent advances in biology and explore their roles and challenges in achieving real applications of artificial LDs in the future.
Topics: Humans; Lipid Droplets; Lipid Metabolism; Endoplasmic Reticulum; Lipids; Metabolic Diseases
PubMed: 37997538
DOI: 10.1002/ctm2.1441 -
Biochemical Pharmacology Nov 2023All human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in... (Review)
Review
All human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in diseases that trigger defects in metabolism, reduced apoptosis, increased proliferation, and progression in almost all tumor types. Metabolic dysregulations and immune dysfunctions are crucial factors in cancer. In this respect, alternative splicing in tumors could be a potential target for therapeutic cancer strategies. Dysregulation of alternative splicing during mRNA maturation promotes carcinogenesis and drug resistance in many cancer types. Alternative splicing (changing the target mRNA 3'UTR binding site) can result in a protein with altered drug affinity, ultimately leading to drug resistance.. Here, we will highlight the function of various alternative splicing factors, how it regulates the reprogramming of cancer cell metabolism, and their contribution to tumor initiation and proliferation. Also, we will discuss emerging therapeutics for treating tumors via abnormal alternative splicing. Finally, we will discuss the challenges associated with these therapeutic strategies for clinical applications.
Topics: Humans; Alternative Splicing; Neoplasms; Carcinogenesis; RNA, Messenger
PubMed: 37813165
DOI: 10.1016/j.bcp.2023.115848 -
Advanced Drug Delivery Reviews Sep 2023The metabolism in eukaryotic cells is a highly ordered system involving various cellular compartments, which fluctuates based on physiological rhythms. Organelles, as... (Review)
Review
The metabolism in eukaryotic cells is a highly ordered system involving various cellular compartments, which fluctuates based on physiological rhythms. Organelles, as the smallest independent sub-cell unit, are important contributors to cell metabolism and drug metabolism, collectively designated intracellular metabolism. However, disruption of intracellular spatiotemporal metabolism can lead to disease development and progression, as well as drug treatment interference. In this review, we systematically discuss spatiotemporal metabolism in cells and cell subpopulations. In particular, we focused on metabolism compartmentalization and physiological rhythms, including the variation and regulation of metabolic enzymes, metabolic pathways, and metabolites. Additionally, the intricate relationship among intracellular spatiotemporal metabolism, metabolism-related diseases, and drug therapy/toxicity has been discussed. Finally, approaches and strategies for intracellular spatiotemporal metabolism analysis and potential target identification are introduced, along with examples of potential new drug design based on this.
Topics: Humans; Organelles; Metabolic Networks and Pathways
PubMed: 37516411
DOI: 10.1016/j.addr.2023.115024