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LKI - Leuven Cancer Institute[Affiliation] Publications | LitMetric

51 results match your criteria: "LKI - Leuven Cancer Institute[Affiliation]"

Article Synopsis
  • Transitioning from a proliferative to an invasive melanoma phenotype increases vulnerability to ferroptosis, but the regulatory circuits behind this susceptibility are unclear.
  • Apolipoprotein E (ApoE) was identified as a key lipid-metabolism gene that helps differentiate between ferroptosis-resistant and sensitive melanoma states by protecting invasive cells from ferroptosis-inducing agents.
  • The study suggests that ApoE secretion and its expression may serve as potential biomarkers for poor response to ferroptosis in melanoma patients.
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Many cancer cells share with yeast a preference for fermentation over respiration, which is associated with overactive glucose uptake and breakdown, a phenomenon called the Warburg effect in cancer cells. The yeast mutant shows even more pronounced hyperactive glucose uptake and phosphorylation causing glycolysis to stall at GAPDH, initiation of apoptosis through overactivation of Ras and absence of growth on glucose. The goal of the present work was to use the yeast strain to screen for novel compounds that would preferentially inhibit overactive glucose influx into glycolysis, while maintaining basal glucose catabolism.

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Humanized mouse models for anti-cancer therapy.

Methods Cell Biol

April 2024

TRACE PDX Platform, LKI Leuven Cancer Institute, Leuven, Belgium; Laboratory of RNA Cancer Biology, Department of Oncology, LKI Leuven Cancer Institute, Leuven, Belgium. Electronic address:

Patient-derived xenograft (PDX) models are the golden standard for preclinical oncology as they can recapitulate the genotypic and phenotypic complexity of human tumors, thus enabling the development of effective therapeutic strategies. PDX models are typically established in immunocompromised animals that allow efficient growth of the xenografted tumor. Given the recent success of immune therapies in different tumors however, the establishment of humanized PDX models is critical to evaluate immune oncology drugs and/or combinations thereof.

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Fatty acid elongation regulates mitochondrial β-oxidation and cell viability in prostate cancer by controlling malonyl-CoA levels.

Biochem Biophys Res Commun

January 2024

South Australian ImmunoGENomics Cancer Institute, Adelaide Medical School and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5005, Australia; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia. Electronic address:

Recently, the fatty acid elongation enzyme ELOVL5 was identified as a critical pro-metastatic factor in prostate cancer, required for cell growth and mitochondrial homeostasis. The fatty acid elongation reaction catalyzed by ELOVL5 utilizes malonyl-CoA as the carbon donor. Here, we demonstrate that ELOVL5 knockdown causes malonyl-CoA accumulation.

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Aim: Chronic kidney disease (CKD) is accompanied by increased cardiovascular risk and heart failure (HF). In rodents, 2,8-dihydroxyadenine (DHA)-induced nephropathy is a frequently used CKD model. Cardiac and kidney tubular cells share high energy demand to guarantee constant contractive force of the heart or reabsorption/secretion of primary filtrated molecules and waste products by the kidney.

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The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood.

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Article Synopsis
  • The study explores the role of the transcription factor CCAAT-enhancer binding protein α (C/EBPα) in lipid metabolism and cellular homeostasis in acute myeloid leukemia (AML), particularly with mutations in FLT3.
  • Researchers found that C/EBPα and FLT3 activation enhance lipid production and desaturation in AML cells, leading to increased vulnerability to oxidative stress.
  • Inhibiting C/EBPα or FLT3 demonstrates potential for therapeutic strategies targeting lipid metabolism to promote ferroptotic cell death in FLT3-mutant AML, a type of leukemia affecting 30% of patients.
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Monounsaturated Fatty Acids: Key Regulators of Cell Viability and Intracellular Signaling in Cancer.

Mol Cancer Res

September 2022

Adelaide Medical School and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide SA, Australia.

Cancer cells feature increased macromolecular biosynthesis to support the formation of new organelles and membranes for cell division. In particular, lipids are key macromolecules that comprise cellular membrane components, substrates for energy generation and mediators of inter- and intracellular signaling. The emergence of more sensitive and accurate technology for profiling the "lipidome" of cancer cells has led to unprecedented leaps in understanding the complexity of cancer metabolism, but also highlighted promising therapeutic vulnerabilities.

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LncRNAs in human cancers: signal from noise.

Trends Cell Biol

July 2022

Laboratory for RNA Cancer Biology, Department of Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Trace, LKI Leuven Cancer Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address:

Given the biochemical reaction stochasticity, the mechanisms leading to conservation of biological functions from noise are obscure. Pervasive transcription of nonconserved genomic regions generates lowly expressed cancer-specific long noncoding RNAs (lncRNAs). How such poorly expressed transcripts, often undetectable in normal tissues, consistently modulate the activity of multiple abundant proteins leading to cancer phenotypes is unclear.

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Article Synopsis
  • FTO is a protein that helps control RNA, and its lower amounts are found in some types of cancer, which may make the cancer worse.
  • When FTO is turned off, it helps cancer cells grow and spread more easily in tests and in living organisms like mice.
  • The study shows that when FTO is less active, it changes how some important genes work, making tumors grow faster and possibly providing a way to treat these cancers better by targeting FTO.
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Article Synopsis
  • Long non-coding RNAs (lncRNAs) like SAMMSON are important because they can help researchers find new treatments for certain cancers.
  • In a study, scientists found that blocking SAMMSON in uveal melanoma cells slowed their growth and made them die, which could help treat this dangerous eye cancer.
  • The research showed that by stopping SAMMSON, cancer cells had trouble making proteins they need to survive, which might lead to new ways to treat patients with this type of cancer.
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Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic settings. However, primary and acquired resistance to chemotherapy in general and platinum-based regimens specifically strongly hampers TNBC management.

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Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the "lipidome" in prostate tumors with matched benign tissues ( = 21), independent unmatched tissues ( = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide ( = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples.

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Optimization of the clofazimine structure leads to a highly water-soluble C3-aminopyridinyl riminophenazine endowed with improved anti-Wnt and anti-cancer activity in vitro and in vivo.

Eur J Med Chem

October 2021

Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, 1206, Geneva, Switzerland; School of Biomedicine, Far Eastern Federal University, 690922, Vladivostok, Russia. Electronic address:

Triple-negative breast cancer (TNBC) is a cancer subtype critically dependent upon excessive activation of Wnt pathway. The anti-mycobacterial drug clofazimine is an efficient inhibitor of canonical Wnt signaling in TNBC, reducing tumor cell proliferation in vitro and in animal models. These properties make clofazimine a candidate to become first targeted therapy against TNBC.

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Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is a common molecular imaging modality used to characterise the abundance and spatial distribution of lipids in situ. There are several technical challenges predominantly involving sample pre-treatment and preparation which have complicated the analysis of clinical tissues by MALDI-MSI. Firstly, the common embedding of samples in optimal cutting temperature (O.

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M(R)apping RNA-Protein Interactions.

Methods Mol Biol

March 2021

Department of Oncology, Laboratory of RNA cancer biology, LKI Leuven Cancer Institute, KU Leuven-University of Leuven, Leuven, Belgium.

The systematic investigation of RNA-protein interactions is a key step towards a better understanding of the functions of RNA molecules.We developed an easy-to-use method to isolate and identify RNAs and proteins bound to long non-coding RNAs (lncRNAs ) in their native configuration. Similar to other methodologies, we utilize biotinylated antisense oligonucleotides (ASOs) to purify the lncRNA of interest and its associated proteins from different cellular compartments.

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ATP13A3 is a major component of the enigmatic mammalian polyamine transport system.

J Biol Chem

August 2021

Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. Electronic address:

Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown.

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Synthesis and fluorine-18 radiolabeling of a phospholipid as a PET imaging agent for prostate cancer.

Nucl Med Biol

February 2021

Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Australia; Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Australia; Department of Medicine, Melbourne University, Melbourne, Australia. Electronic address:

Introduction: Altered lipid metabolism and subsequent changes in cellular lipid composition have been observed in prostate cancer cells, are associated with poor clinical outcome, and are promising targets for metabolic therapies. This study reports for the first time on the synthesis of a phospholipid radiotracer based on the phospholipid 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine (PC44:12) to allow tracking of polyunsaturated lipid tumor uptake via PET imaging. This tracer may aid in the development of strategies to modulate response to therapies targeting lipid metabolism in prostate cancer.

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In cancer, upregulation of coinhibitory B7 ligands has been associated with immune evasion. So far, anti-programmed death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies have been used in immuno-oncology, with promising outcomes; however, it is still needed to identify other markers, especially for endometrial cancer (EC). EC is a gynecological malignancy historically classified into two types: type I, with mostly estrogen-dependent endometrioid diseases, and the most aggressive type II, including mainly estrogen-independent and non-endometrioid tumors.

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Background & Aims: The micronutrient zinc is essential for proper immune function. Consequently, zinc deficiency leads to impaired immune function, as seen in decreased secretion of interleukin (IL)-2 by T cells. Although this association has been known since the late 1980s, the underlying molecular mechanisms are still unknown.

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Lipogenic effects of androgen signaling in normal and malignant prostate.

Asian J Urol

July 2020

Adelaide Medical School and Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, Australia.

Prostate cancer is an androgen-dependent cancer with unique metabolic features compared to many other solid tumors, and typically does not exhibit the "Warburg effect". During malignant transformation, an early metabolic switch diverts the dependence of normal prostate cells on aerobic glycolysis for the synthesis of and secretion of citrate towards a more energetically favorable metabolic phenotype, whereby citrate is actively oxidised for energy and biosynthetic processes ( lipogenesis). It is now clear that lipid metabolism is one of the key androgen-regulated processes in prostate cells and alterations in lipid metabolism are a hallmark of prostate cancer, whereby increased lipogenesis accompanied by overexpression of lipid metabolic genes are characteristic of primary and advanced disease.

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Fatty acid β-oxidation (FAO) is the main bioenergetic pathway in human prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate therapeutic efficacy of targeting FAO in clinical prostate tumors cultured ex vivo, and identify encoding the rate-limiting enzyme for oxidation of polyunsaturated fatty acids (PUFAs), as robustly overexpressed in PCa tissues and associated with shorter relapse-free survival. is a negatively-regulated androgen receptor (AR) target gene and, therefore, may promote PCa cell survival and resistance to AR targeting therapeutics.

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Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer.

Cancer Metab

June 2020

Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Princess Alexandra Hospital, Translational Research Institute, Brisbane, Australia.

Background: Metabolic reprograming, non-mutational epigenetic changes, increased cell plasticity, and multidrug tolerance are early hallmarks of therapy resistance in cancer. In this temporary, therapy-tolerant state, cancer cells are highly sensitive to ferroptosis, a form of regulated cell death that is caused by oxidative stress through excess levels of iron-dependent peroxidation of polyunsaturated fatty acids (PUFA). However, mechanisms underpinning therapy-induced ferroptosis hypersensitivity remain to be elucidated.

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An okadaic acid fragment analogue prevents nicotine-induced resistance to cisplatin by recovering PP2A activity in non-small cell lung cancer cells.

Bioorg Chem

July 2020

Department of Pharmacology and Therapeutic, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, C/ Diego de León, 62, 28006 Madrid, Spain. Electronic address:

We herein report the design, synthesis, and functional impact of an okadaic acid (OA) small analogue, ITH12680, which restores the activity of phosphoprotein phosphatase 2A (PP2A), whose deficient activity has been implicated in nicotine-mediated tumor progression and chemoresistance in non-small cell lung cancer (NSCLC). For its design, we paid attention to the structure of the PP2A-OA complex, where the C16-C38 OA fragment confers PP2A affinity and selectivity, but it is not involved in the inhibitory effect. Confirming this hypothesis, PP2A activity was not inhibited by ITH12680.

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