bims-medica Biomed News
on Metabolism and diet in cancer
Issue of 2024‒08‒25
seventeen papers selected by
Brett Chrest, East Carolina University
  1. Excessive lipid production shapes glioma tumor microenvironment.
  2. The critical role of glutamine and fatty acids in the metabolic reprogramming of anoikis-resistant melanoma cells.
  3. Gene Expression of Glycolysis Enzymes in MCF-7 Breast Cancer Cells Exposed to Warburg Effect and Hypoxia.
  4. Glycolysis and chemoresistance in acute myeloid leukemia.
  5. Diet and physical activity advice for colorectal cancer survivors: critical synthesis of public-facing guidance.
  6. Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.
  7. Aerobic glycolysis but not GLS1-dependent glutamine metabolism is critical for anti-tumor immunity and response to checkpoint inhibition.
  8. Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.
  9. Cell fate simulation reveals cancer cell features in the tumor microenvironment.
  10. Trametinib potentiates anti-PD-1 efficacy in tumors established from chemotherapy-primed pancreatic cancer cells.
  11. The role of the primitive marker CD133 in CD34-negative acute myeloid leukemia for the detection of leukemia stem cells.
  12. Short-term post-fast refeeding enhances intestinal stemness via polyamines.
  13. Cells poised to divide can delay their commitment to proliferate.
  14. The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review.
  15. Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.
  16. Metabolomic Profiling of Tumor Tissues Unveils Metabolic Shifts in Non-Small Cell Lung Cancer Patients with Concurrent Diabetes Mellitus.
  17. Venetoclax for pediatric patients with newly diagnosed acute myeloid leukemia.
  1. Ultrastruct Pathol. 2024 Aug 19. 1-11
    Excessive lipid production shapes glioma tumor microenvironment.
    Haitham H Maraqah, John Paul Aboubechara, Mones S Abu-Asab, Han Sung Lee, Orwa Aboud.
      Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n = 18) and IDH1 mutant (IDH1-mt) astrocytoma (n = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals.
    Keywords:  Astrocytoma; glioblastoma; glycolysis; immune evasion; lipid accumulation; mitochondrial dysfunction; oxidative phosphorylation; therapeutic strategies; tumor microenvironment; ultrastructural analysis
    DOI:  https://doi.org/10.1080/01913123.2024.2392728
  2. Front Pharmacol. 2024 ;15 1422281
    The critical role of glutamine and fatty acids in the metabolic reprogramming of anoikis-resistant melanoma cells.
    S Peppicelli, T Kersikla, G Menegazzi, E Andreucci, J Ruzzolini, C Nediani, F Bianchini, L Calorini.
      Introduction: Circulating tumor cells (CTCs) represent the sub-population of cells shed into the vasculature and able to survive in the bloodstream, adhere to target vascular endothelial cells, and re-growth into the distant organ. CTCs have been found in the blood of most solid tumor-bearing patients and are used as a diagnostic marker. Although a complex genotypic and phenotypic signature characterizes CTCs, the ability to survive in suspension constitutes the most critical property, known as resistance to anoikis, e.g., the ability to resist apoptosis resulting from a loss of substrate adhesion. Here, we selected melanoma cells resistant to anoikis, and we studied their metabolic reprogramming, with the aim of identifying new metabolic targets of CTCs. Methods: Subpopulations of melanoma cells expressing a high anoikis-resistant phenotype were selected by three consecutive rocking exposures in suspension and studied for their phenotypic and metabolic characteristics. Moreover, we tested the efficacy of different metabolic inhibitors targeting glycolysis (2DG), LDHA (LDHA-in-3), the mitochondrial electron transport chain complex I (rotenone), glutaminase (BPTES), fatty acid transporter (SSO), fatty acid synthase (denifanstat), CPT1 (etomoxir), to inhibit cell survival and colony formation ability after 24 h of rocking condition. Results: Anoikis-resistant cells displayed higher ability to grow in suspension on agarose-covered dishes respect to control cells, and higher cell viability and colony formation capability after a further step in rocking condition. They showed also an epithelial-to-mesenchymal transition associated with high invasiveness and a stemness-like phenotype. Anoikis-resistant melanoma cells in suspension showed a metabolic reprogramming from a characteristic glycolytic metabolism toward a more oxidative metabolism based on the use of glutamine and fatty acids, while re-adhesion on the dishes reversed the metabolism to glycolysis. The treatment with metabolic inhibitors highlighted the effectiveness of rotenone, BPTES, SSO, and etomoxir in reducing the viability and the colony formation ability of cells capable of surviving in suspension, confirming the dependence of their metabolism on oxidative phosphorylation, using glutamine and fatty acids as the most important fuels. Discussion: This finding opens up new therapeutic strategies based on metabolic inhibitors of glutaminase and fatty acid oxidation for the treatment of CTCs and melanoma metastases.
    Keywords:  anoikis resistance; cell metabolism; circulating tumor cells; melanoma; therapy
    DOI:  https://doi.org/10.3389/fphar.2024.1422281
  3. Int J Mol Cell Med. 2024 ;13(1): 29-45
    Gene Expression of Glycolysis Enzymes in MCF-7 Breast Cancer Cells Exposed to Warburg Effect and Hypoxia.
    Irem Bayar, Gamze Sevri Ekren Asici, Ayşegül Bildik, Funda Kiral.
      Hypoxia can cause significant changes in the glucose metabolism of cancer cells that prefer aerobic glycolysis for energy production instead of the conventional oxidative phosphorylation mechanism. In this study, breast cancer cells (MCF-7) were exposed to glucose (0-5.5-15-55 mM), during specific incubation periods (3, 6, 12, or 24 hours) under normoxic and hypoxic conditions. The expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and glycolytic enzymes at varying glucose concentrations in cells were investigated in the different oxygen environments. It was determined that glycolytic enzymes [Hexokinase 2 (HK2), Pyruvate Kinase M2 (PKM2), Glucose-6-phosphate dehydrogenase (G6PD), Lactate Dehydrogenase A (LDHA), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), and Phosphofructokinase M (PFKM)] increased at the transcriptional level, especially in the first hours. This increase indicates that major metabolic reprogramming in response to hypoxia probably occurs over a short period of time. The increase in G6PD gene expression under high glucose and hypoxia conditions suggests that the pentose phosphate pathway (PPP) is used by cancer cells to synthesize necessary precursors for the cell. The results of the study showed that there is a significant interaction between hypoxia and glycolytic metabolism in cancer cells. It is thought that metabolic pathways activated by hypoxia and related genes located in these pathways will contribute to the literature by offering the potential to be target molecules for therapeutic purposes.
    Keywords:  Glucose; MCF-7; gene expression; glycolysis; hypoxia; normoxia
    DOI:  https://doi.org/10.22088/IJMCM.BUMS.13.1.29
  4. Heliyon. 2024 Aug 15. 10(15): e35721
    Glycolysis and chemoresistance in acute myeloid leukemia.
    Yan Yang, Jianlin Pu, You Yang.
      While traditional high-dose chemotherapy can effectively prolong the overall survival of acute myeloid leukemia (AML) patients and contribute to better prognostic outcomes, the advent of chemoresistance is a persistent challenge to effective AML management in the clinic. The therapeutic resistance is thought to emerge owing to the heterogeneous and adaptable nature of tumor cells when exposed to exogenous stimuli. Recent studies have focused on exploring metabolic changes that may afford novel opportunities to treat AML, with a particular focus on glycolytic metabolism. The Warburg effect, a hallmark of cancer, refers to metabolism of glucose through glycolysis under normoxic conditions, which contributes to the development of chemoresistance. Despite the key significance of this metabolic process in the context of malignant transformation, the underlying molecular mechanisms linking glycolysis to chemoresistance in AML remain incompletely understood. This review offers an overview of the current status of research focused on the relationship between glycolytic metabolism and AML resistance to chemotherapy, with a particular focus on the contributions of glucose transporters, key glycolytic enzymes, signaling pathways, non-coding RNAs, and the tumor microenvironment to this relationship. Together, this article will provide a foundation for the selection of novel therapeutic targets and the formulation of new approaches to treating AML.
    Keywords:  Acute myeloid leukemia; Chemoresistance; Glycolysis
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e35721
  5. Support Care Cancer. 2024 Aug 22. 32(9): 609
    Diet and physical activity advice for colorectal cancer survivors: critical synthesis of public-facing guidance.
    Anna Fretwell, Christina Dobson, Samuel T Orange, Bernard M Corfe.
      PURPOSE: Colorectal cancer (CRC) survivors report that diet and physical activity guidance from healthcare professionals following discharge from care is limited. Survivors seek advice from alternative sources. This study critically synthesised the English language diet and physical activity guidance available online for CRC survivors.METHODS: We conducted an internet search to identify national cancer organisations (NCO) in countries with high CRC incidence rates. We searched NCO website content for guidance related to diet and physical activity. Recommendations were categorised by cancer phase (prevention/survivorship), cancer type, and the intended outcome (health or cancer-control-CRC recurrence/CRC-specific mortality). A synthesised guideline was derived from recommendations consistently made by at least half of the sources.
    RESULTS: We identified 12 NCOs from six countries, by whom 27 diet and physical activity recommendations were made. For CRC prevention, over 80% of recommendations were aimed at improving cancer-control outcomes. For CRC survivorship, less than 40% of recommendations were aimed at improving cancer-control outcomes. Physical activity was the only recommendation present on more than 50% of NCO websites aimed at improving cancer-control outcomes for CRC survivorship.
    CONCLUSION: Diet and physical activity guidance for CRC survivors on NCO websites is limited and primarily based on recommendations for improving general health, not improving cancer-control outcomes. NCO websites frequently refer survivors to primary prevention guidance, potentially reflecting the lack of evidence specific to CRC survivorship. There is a need for diet and physical activity advice for survivors that is evidence-based, comprehensive, and consistent across organisations and tailored to specific cancer sites.
    Keywords:  Colorectal cancer survivor; Diet; Health information; Physical activity
    DOI:  https://doi.org/10.1007/s00520-024-08797-5
  6. Cell Rep. 2024 Aug 20. pii: S2211-1247(24)01014-3. [Epub ahead of print]43(9): 114663
    Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.
    Heidi H Pak, Allison N Grossberg, Rachel R Sanderfoot, Reji Babygirija, Cara L Green, Mikaela Koller, Monika Dzieciatkowska, Daniel A Paredes, Dudley W Lamming.
      Calorie restriction (CR) extends lifespan and healthspan in diverse species. Comparing ad libitum- and CR-fed mice is challenging due to their significantly different feeding patterns, with CR-fed mice consuming their daily meal in 2 h and then subjecting themselves to a prolonged daily fast. Here, we examine how ad libitum- and CR-fed mice respond to tests performed at various times and fasting durations and find that the effects of CR-insulin sensitivity, circulating metabolite levels, and mechanistic target of rapamycin 1 (mTORC1) activity-result from the specific temporal conditions chosen, with CR-induced improvements in insulin sensitivity observed only after a prolonged fast, and the observed differences in mTORC1 activity between ad libitum- and CR-fed mice dependent upon both fasting duration and the specific tissue examined. Our results demonstrate that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.
    Keywords:  CP: Metabolism; aging; calorie restriction; dietary restriction; fasting; lifespan; mTOR; time-restricted feeding
    DOI:  https://doi.org/10.1016/j.celrep.2024.114663
  7. Cell Rep. 2024 Aug 18. pii: S2211-1247(24)00982-3. [Epub ahead of print]43(8): 114632
    Aerobic glycolysis but not GLS1-dependent glutamine metabolism is critical for anti-tumor immunity and response to checkpoint inhibition.
    Patrick M Gubser, Sharanya Wijesinghe, Leonie Heyden, Sarah S Gabriel, David P de Souza, Christoph Hess, Malcolm M McConville, Daniel T Utzschneider, Axel Kallies.
      Tumor cells undergo uncontrolled proliferation driven by enhanced anabolic metabolism including glycolysis and glutaminolysis. Targeting these pathways to inhibit cancer growth is a strategy for cancer treatment. Critically, however, tumor-responsive T cells share metabolic features with cancer cells, making them susceptible to these treatments as well. Here, we assess the impact on anti-tumor T cell immunity and T cell exhaustion by genetic ablation of lactate dehydrogenase A (LDHA) and glutaminase1 (GLS1), key enzymes in aerobic glycolysis and glutaminolysis. Loss of LDHA severely impairs expansion of T cells in response to tumors and chronic infection. In contrast, T cells lacking GLS1 can compensate for impaired glutaminolysis by engaging alternative pathways, including upregulation of asparagine synthetase, and thus efficiently respond to tumor challenge and chronic infection as well as immune checkpoint blockade. Targeting GLS1-dependent glutaminolysis, but not aerobic glycolysis, may therefore be a successful strategy in cancer treatment, particularly in combination with immunotherapy.
    Keywords:  CP: Cancer; CP: Metabolism; GLS1; LDHA; Tpex
    DOI:  https://doi.org/10.1016/j.celrep.2024.114632
  8. Front Pharmacol. 2024 ;15 1409210
    Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.
    Monika Chomczyk, Luca Gazzola, Shubhankar Dash, Patryk Firmanty, Binsah S George, Vakul Mohanty, Hussein A Abbas, Natalia Baran.
      Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML cases. These mutations form an important molecular subgroup, and patients with these mutations have the worst prognosis and shortest overall survival among patients with AML, even when treated with aggressive chemotherapy and allogeneic stem cell transplant. The frequency of TP53-mutations increases in relapsed and recurrent AML and is associated with chemoresistance. Progress in AML genetics and biology has brought the novel therapies, however, the clinical benefit of these agents for patients whose disease is driven by TP53 mutations remains largely unexplored. This review focuses on the molecular characteristics of TP53-mutated disease; the impact of TP53 on selected hallmarks of leukemia, particularly metabolic rewiring and immune evasion, the clinical importance of TP53 mutations; and the current progress in the development of preclinical and clinical therapeutic strategies to treat TP53-mutated disease.
    Keywords:  AML; TP53 mutations; drug resistance; immunosuppression; metabolic rewiring; therapeutic approaches
    DOI:  https://doi.org/10.3389/fphar.2024.1409210
  9. J Biol Chem. 2024 Aug 20. pii: S0021-9258(24)02198-7. [Epub ahead of print] 107697
    Cell fate simulation reveals cancer cell features in the tumor microenvironment.
    Sachiko Sato, Ann Rancourt, Masahiko S Satoh.
      To elucidate the dynamic evolution of cancer cell characteristics within the tumor microenvironment (TME), we developed an integrative approach combining single-cell tracking, cell fate simulation, and three-dimensional (3D) TME modeling. We began our investigation by analyzing the spatiotemporal behavior of individual cancer cells in cultured pancreatic (MiaPaCa2) and cervical (HeLa) cancer cell lines, with a focus on the α2-6 sialic acid (α2-6Sia) modification on glycans, which is associated with cell stemness. Our findings revealed that MiaPaCa2 cells exhibited significantly higher levels of α2-6Sia modification, correlating with enhanced reproductive capabilities, whereas HeLa cells showed less prevalence of this modification. To accommodate the in vivo variability of α2-6Sia levels, we employed a cell fate simulation algorithm that digitally generates cell populations based on our observed data while varying the level of sialylation, thereby simulating cell growth patterns. Subsequently, we performed a 3D TME simulation with these deduced cell populations, considering the microenvironment that could impact cancer cell growth. Immune cell landscape information derived from 193 cervical and 172 pancreatic cancer cases was used to estimate the degree of the positive or negative impact. Our analysis suggests that the deduced cells generated based on the characteristics of MiaPaCa2 cells are less influenced by the immune cell landscape within the TME compared to those of HeLa cells, highlighting that the fate of cancer cells is shaped by both the surrounding immune landscape and the intrinsic characteristics of the cancer cells.
    Keywords:  3-dimensional tumor microenvironment simulation; Sambucus nigra lectin; Single-cell tracking; cancer cell heterogeneity; cancer cell lines; cell fate simulation; cervical cancer; live cell imaging; pancreatic cancer; stemness; tumor microenvironment; α2-6 sialic acid modification on glycans
    DOI:  https://doi.org/10.1016/j.jbc.2024.107697
  10. Mol Cancer Ther. 2024 Aug 20.
    Trametinib potentiates anti-PD-1 efficacy in tumors established from chemotherapy-primed pancreatic cancer cells.
    Thao D Pham, Anastasia E Metropulos, Nida Mubin, Jeffrey H Becker, Dhavan Shah, Christina Spaulding, Mario A Shields, David J Bentrem, Hidayatullah G Munshi.
      Despite advances in immune checkpoint inhibitors (ICIs), chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX (5-fluorouracil (5FU), irinotecan, and oxaliplatin) regimen, and ICIs have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in PDAC patients. In this study, we report that neoadjuvant FOLFRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of 5FU (F), irinotecan (I), and oxaliplatin (O) (FIO). In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with 6-8 cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a pro-inflammatory immune profile similar to human PDAC tumors following neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor Trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining Trametinib and anti-PD-1 antibodies in PDAC patients following neoadjuvant or short-term FOLFIRINOX treatment to achieve effective anti-tumor responses.
    DOI:  https://doi.org/10.1158/1535-7163.MCT-23-0833
  11. Cytometry B Clin Cytom. 2024 Aug 23.
    The role of the primitive marker CD133 in CD34-negative acute myeloid leukemia for the detection of leukemia stem cells.
    Tom Reuvekamp, Luca L G Janssen, Lok Lam Ngai, Jannemieke Carbaat-Ham, Daphne den Hartog, Willemijn J Scholten, Angèle Kelder, Diana Hanekamp, Eliza Wensink, Noortje van Gils, Patrycja Gradowska, Bob Löwenberg, Gert J Ossenkoppele, Arjan A van de Loosdrecht, Theresia M Westers, Linda Smit, Costa Bachas, Jacqueline Cloos.
      The most important reason for dismal outcomes in acute myeloid leukemia (AML) is the development of relapse. Leukemia stem cells (LSCs) are hypothesized to initiate relapse, and high CD34+CD38- LSC load is associated with poor prognosis. In 10% of AML patients, CD34 is not or is low expressed on the leukemic cells (<1%), and CD34+CD38- LSCs are absent. These patients are classified as CD34-negative. We aimed to determine whether the primitive marker CD133 can detect LSCs in CD34-negative AML. We retrospectively quantified 148 CD34-negative patients for proportions of CD34-CD133+ and CD133+CD38- cell fractions in the diagnostic samples of CD34-negative patients in the HOVON102 and HOVON132 trials. No prognostic difference was found between patients with high or low proportions of CD34-CD133+, which is found to be aberrantly expressed in AML. A high level of CD133+CD38- cells was not associated with poor overall survival, and expression in AML was similar to normal bone marrow. To conclude, CD133 is useful as an additional primitive marker for the detection of leukemic blast cells in CD34-negative AML. However, CD133+CD38 alone is not suitable for the detection of LSCs at diagnosis.
    Keywords:  CD133; acute myeloid leukemia; flow cytometry; leukemia stem cells; measurable residual disease
    DOI:  https://doi.org/10.1002/cyto.b.22201
  12. Nature. 2024 Aug 21.
    Short-term post-fast refeeding enhances intestinal stemness via polyamines.
    Shinya Imada, Saleh Khawaled, Heaji Shin, Sven W Meckelmann, Charles A Whittaker, Renan Oliveira Corrêa, Chiara Alquati, Yixin Lu, Guodong Tie, Dikshant Pradhan, Gizem Calibasi-Kocal, Luiza Martins Nascentes Melo, Gabriele Allies, Jonas Rösler, Pia Wittenhofer, Jonathan Krystkiewicz, Oliver J Schmitz, Jatin Roper, Marco Aurelio Ramirez Vinolo, Luigi Ricciardiello, Evan C Lien, Matthew G Vander Heiden, Ramesh A Shivdasani, Chia-Wei Cheng, Alpaslan Tasdogan, Ömer H Yilmaz.
      For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans1-6. However, how fasting and post-fast refeeding affect adult stem cells and tumour formation has yet to be explored in depth. Here we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation; post-fast refeeding augments the regenerative capacity of Lgr5+ ISCs, and loss of the tumour suppressor gene Apc in post-fast-refed ISCs leads to a higher tumour incidence in the small intestine and colon than in the fasted or ad libitum-fed states, demonstrating that post-fast refeeding is a distinct state. Mechanistically, we discovered that robust mTORC1 induction in post-fast-refed ISCs increases protein synthesis via polyamine metabolism to drive these changes, as inhibition of mTORC1, polyamine metabolite production or protein synthesis abrogates the regenerative or tumorigenic effects of post-fast refeeding. Given our findings, fast-refeeding cycles must be carefully considered and tested when planning diet-based strategies for regeneration without increasing cancer risk, as post-fast refeeding leads to a burst in stem-cell-driven regeneration and tumorigenicity.
    DOI:  https://doi.org/10.1038/s41586-024-07840-z
  13. Nature. 2024 Aug 21.
    Cells poised to divide can delay their commitment to proliferate.
      
    Keywords:  Cancer; Cell biology
    DOI:  https://doi.org/10.1038/d41586-024-02640-x
  14. Int J Biol Macromol. 2024 Aug 16. pii: S0141-8130(24)05640-X. [Epub ahead of print] 134835
    The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review.
    Leisheng Wang, Shiwei Xu, Mengzhen Zhou, Hao Hu, Jinyou Li.
      Fatty acid metabolism is a complex biochemical process, including the production, breakdown and application of fatty acids. Not only is it an important component of lipid metabolism, fatty acid metabolism is also connected to the energy metabolism pathways of cells and plays a vital role in maintaining the energy balance of organisms. Diacylglycerol-O-acyltransferase 1 (DGAT1) and Diacylglycerol-O-acyltransferase 2 (DGAT2) are key components in regulating lipid metabolism, which provide energy for cell proliferation and growth. Recent studies have shown that DGAT1 and DGAT2 influence tumor progression through fatty acid metabolism in cancer. Although DGAT1 and DGAT2 have similar names, they differ significantly in various aspects and play distinct roles in individual tumors. A comparative analysis of the physiological roles of these enzymes and their differential expressions in different types of tumors will enhance our understanding of their unique characteristics. This article summarizes the characteristics of tumor fatty acid metabolism and explains how DGAT1 and DGAT2 specifically promote tumor progression. In addition, this review discusses the potential of lipid-lowering drugs in tumor treatment, providing a new perspective on targeting fatty acid metabolism to inhibit tumor progression in the future, while emphasizing the importance of DGAT1 and DGAT2 as potential targets for tumor treatment.
    Keywords:  Cancer; DGAT1; DGAT2; Fatty acid metabolism
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.134835
  15. Recent Pat Anticancer Drug Discov. 2024 Aug 21.
    Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.
    Ali Raza Ishaq, Tahira Younis, Shankun Lin, Muhammad Usman, Tingfang Wang, Zhe-Sheng Chen.
      Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms "PFK-1", "PFKP-1", "PFKL-1", "PFKM-1", "PFKM-1 and cancer", "PFKP-1 and cancer", "PFKL-1 and cancer", and "inhibitors of PFK-1" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and β-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment.
    Keywords:  PFK-1; cancer; genetic/pharmacologic inhibitors.; therapeutic targets; tumor progression
    DOI:  https://doi.org/10.2174/0115748928321372240813080131
  16. J Proteome Res. 2024 Aug 20.
    Metabolomic Profiling of Tumor Tissues Unveils Metabolic Shifts in Non-Small Cell Lung Cancer Patients with Concurrent Diabetes Mellitus.
    Xiaohong Lyu, Yujue Wang, Yuan Xu, Zhewei Zhao, Hongsheng Liu, Zeping Hu.
      A comprehensive understanding of the exact influence of type 2 diabetes mellitus (T2DM) on the metabolic status of non-small cell lung cancer (NSCLC) is still lacking. This study explores metabolic alterations in tumor tissues among patients with coexisting NSCLC and T2DM in comparison with NSCLC patients. A combined approach of clinical analysis and metabolomics was employed, including 20 NSCLC patients and 20 NSCLC+T2DM patients. Targeted metabolomics analysis was performed on tumor tissues using the liquid chromatography-mass spectrometry (LC-MS) approach. A clear segregation was observed between NSCLC+T2DM and matched NSCLC tissue samples in Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA). Furthermore, the levels of 7 metabolites are found to be significantly different between diabetes/nondiabetes tumor tissue samples. The related pathways included arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, purine metabolism, biotin metabolism, and histidine metabolism. 3-Phenyllactic acid, carnitine-C5, carnitine-C12, and serotonin showed a positive linear correlation with fasting blood glucose levels in NSCLC patients. Uridine, pipecolic acid, cytosine, and fasting blood glucose levels were found to have a negative correlation. Our results suggest that NSCLC patients with concurrent T2DM exhibit distinct metabolic shifts in tumor tissues compared to those of solely NSCLC patients.
    Keywords:  diabetes; metabolites; metabolomics; non-small cell lung cancer
    DOI:  https://doi.org/10.1021/acs.jproteome.3c00924
  17. Pediatr Blood Cancer. 2024 Aug 16. e31286
    Venetoclax for pediatric patients with newly diagnosed acute myeloid leukemia.
    Amber Gibson, Samantha Dickson, David McCall, Miriam Garcia, Jeremy Connors, Jiasen He, Michael Roth, Cesar Nunez, Branko Cuglievan.
      This retrospective study at the University of Texas MD Anderson Cancer Center evaluated frontline venetoclax combination therapy in 11 pediatric/adolescent patients with acute myeloid leukemia (AML). Despite the small sample size and retrospective nature, the treatment demonstrated safety and potential efficacy, with most patients achieving early complete remission. Adverse events were consistent with other AML therapies, and no discontinuations due to toxicity occurred. While acknowledging study limitations, including selection bias and diverse concurrent therapies, this research underscores the promising role of venetoclax in pediatric AML. Further investigation is crucial to validate its long-term efficacy in this population.
    Keywords:  acute myeloid leukemia; pediatric; venetoclax
    DOI:  https://doi.org/10.1002/pbc.31286
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