Mitochondria as a Novel Target for Cancer Chemoprevention: Emergence of Mitochondrial-targeting Agents

Cancer Prevention Research, Journal Year: 2020, Volume and Issue: 14(3), P. 285 - 306

Published: Dec. 10, 2020

Abstract Cancer chemoprevention is the most effective approach to control cancer in population. Despite significant progress, has not been widely adopted because agents that are safe tend be less and those highly toxic. Thus, there an urgent need develop novel chemopreventive agents, such as mitochondria-targeted can prevent prolong survival. Mitochondria, central site for cellular energy production, have important functions cell survival death. Several studies revealed a role mitochondrial metabolism promoting development progression, making mitochondria promising new target prevention. Conjugating delocalized lipophilic cations, triphenylphosphonium cation (TPP+), compounds of interest targeting. The hyperpolarized tumor membrane potential allow selective accumulation TPP+ conjugates versus normal cells. This could enhance direct killing precancerous, dysplastic, cells while minimizing toxicities

Language: Английский

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Mitochondria-centric bioenergetic characteristics in cancer stem-like cells

Archives of Pharmacal Research, Journal Year: 2019, Volume and Issue: 42(2), P. 113 - 127

Published: Feb. 1, 2019

Metabolic and genotoxic stresses that arise during tumor progression anti-cancer treatment, respectively, can impose a selective pressure to promote cancer evolution in the microenvironment. This process ultimately selects for most "fit" clones, which generally have stem cell like phenotype with features of drug resistance, epithelial-mesenchymal transition, invasiveness, high metastatic potential. From bioenergetics perspective, these stem-like cells (CSCs) exhibit mitochondria-centric energy metabolism are capable opportunistically utilizing available nutrients such as fatty acids generate ATP other metabolic substances, providing advantage their survival an impermissible environment context. Thus, diverse therapeutic strategies needed efficiently tackle CSCs eliminate advantage. Here, we review bioenergetic characteristics vulnerabilities specific CSCs, provide unprecedented opportunity curb CSC-driven mortality rates. We particularly focus on potential CSC bioenergetics-targeted strategy versatile component treatment modalities applicable types. A expand inventory combinatorial regimens current armamentarium.

Language: Английский

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Mass spectrometry imaging to detect lipid biomarkers and disease signatures in cancer

Cancer Reports, Journal Year: 2019, Volume and Issue: 2(6)

Published: Dec. 1, 2019

Abstract Background Current methods to identify, classify, and predict tumor behavior mostly rely on histology, immunohistochemistry, molecular determinants. However, better predictive markers are required for diagnosis evaluation. Due, in part, recent technological advancements, metabolomics lipid biomarkers have become a promising area cancer research. Therefore, there is necessity novel complementary techniques identify visualize these within tumors surrounding tissue. Recent Findings Since its introduction, mass spectrometry imaging (MSI) has proven be powerful tool mapping analytes biological tissues. By adding the label‐free specificity of detailed spatial information traditional hundreds lipids can imaged simultaneously tumor. MSI provides highly maps comparing intra‐tumor, margin, healthy regions biomarkers, patterns disease, potential therapeutic targets. In this manuscript, advancement sample preparation technologies discussed with special emphasis research biomarkers. Conclusion offers unique approach biomolecular characterization tissues valuable histology biomarker discovery classification clinical applications.

Language: Английский

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Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Cancers, Journal Year: 2020, Volume and Issue: 12(1), P. 253 - 253

Published: Jan. 20, 2020

Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact HPV status on HNSCC remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique HPV-positive influences survival. The Cancer Genome Atlas RNA-seq data from primary samples were categorized as 73 HPV-positive, 442 HPV-negative, 43 normal-adjacent control tissues. analyzed 229 metabolic genes identified numerous differentially expressed between negative patients. exhibited lower levels involved in glycolysis higher tricarboxylic acid cycle, oxidative phosphorylation, β-oxidation than HPV-negative carcinomas. Importantly, reduced SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, SLC16A2 correlated with improved survival only group. This work suggests specific transcriptional alterations may serve predictive biomarkers outcome identifies potential targets for novel therapeutic intervention cancers.

Language: Английский

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The Role of Lipid Metabolism in Gastric Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: June 15, 2022

Gastric cancer has been one of the most common cancers worldwide with extensive metastasis and high mortality. Chemotherapy found as a main treatment for metastatic gastric cancer, whereas drug resistance limits effectiveness chemotherapy leads to failure. in complex multifactorial mechanism, among which lipid metabolism plays vital role. Increased synthesis new lipids or uptake exogenous can facilitate rapid growth cells tumor formation. Lipids form structural basis biofilms while serving signal molecules energy sources. It is noteworthy that capable inducing by reshaping micro-environment. In this study, mechanisms metabolic pathways correlated are reviewed. particular, we discuss effects on autophagy, biomarkers from perspective metabolism. brief, insights be gained into development promising therapies through an in-depth investigation mechanism reprogramming resensitization cells, scientific provided applying lipid-key enzyme inhibitors chemical sensitizers clinical settings.

Language: Английский

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