Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer

Ansari, Rokaya El ; Craze, Madeleine L. ; Althobiti, Maryam ; Alfarsi, Lutfi ; Ellis, Ian O. ; Rakha, Emad A. ; Green, Andrew R.

Cancer cells must alter their metabolism to support proliferation. Immune evasion also plays a role in supporting tumour progression. This study aimed to find whether enhanced glutamine uptake in breast cancer (BC) can derive the existence of specific immune cell subtypes, including the subsequent impact on patient outcome.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Window of opportunity clinical trial designs to study cancer metabolism

Aroldi, Francesca ; Lord, Simon R.

Window of opportunity trials exploit the ‘window’ of time after cancer diagnosis, typically prior to initiation of cancer therapy. In recent years this study design has become a more regular feature of drug development, as this ‘window’ provides an opportunity to carry out a thorough pharmacodynamic assessment of a therapy of interest in tumours that are unperturbed by prior treatment. Many of the first window trials interrogated the bioactivity of drugs being repurposed for cancer treatment, [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Carbonic anhydrase IX and acid transport in cancer

Becker, Holger M.

Alterations in tumour metabolism and acid/base regulation result in the formation of a hostile environment, which fosters tumour growth and metastasis. Acid/base homoeostasis in cancer cells is governed by the concerted interplay between carbonic anhydrases (CAs) and various transport proteins, which either mediate proton extrusion or the shuttling of acid/base equivalents, such as bicarbonate and lactate, across the cell membrane. Accumulating evidence suggests that some of these transporters [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Kinetic modelling of quantitative proteome data predicts metabolic reprogramming of liver cancer

Berndt, Nikolaus ; Egners, Antje ; Mastrobuoni, Guido ; Vvedenskaya, Olga ; Fragoulis, Athanassios ; Dugourd, Aurélien ; Bulik, Sascha ; Pietzke, Matthias ; Bielow, Chris ; van Gassel, Rob ; Damink, Steven W. Olde ; Erdem, Merve ; Saez-Rodriguez, Julio ; Holzhütter, Hermann-Georg ; Kempa, Stefan ; Cramer, Thorsten

Metabolic alterations can serve as targets for diagnosis and cancer therapy. Due to the highly complex regulation of cellular metabolism, definite identification of metabolic pathway alterations remains challenging and requires sophisticated experimentation.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma

Björkblom, Benny ; Jonsson, Pär ; Tabatabaei, Pedram ; Bergstrom, Per ; Johansson, Mikael ; Asklund, Thomas ; Bergenheim, A. Tommy ; Antti, Henrik

High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Aconitase 2 inhibits the proliferation of MCF-7 cells promoting mitochondrial oxidative metabolism and ROS/FoxO1-mediated autophagic response

Ciccarone, Fabio ; Di Leo, Luca ; Lazzarino, Giacomo ; Maulucci, Giuseppe ; Di Giacinto, Flavio ; Tavazzi, Barbara ; Ciriolo, Maria Rosa

Deregulation of the tricarboxylic acid cycle (TCA) due to mutations in specific enzymes or defective aerobic metabolism is associated with tumour growth. Aconitase 2 (ACO2) participates in the TCA cycle by converting citrate to isocitrate, but no evident demonstrations of its involvement in cancer metabolism have been provided so far.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Increased inflammatory lipid metabolism and anaplerotic mitochondrial activation follow acquired resistance to vemurafenib in BRAF-mutant melanoma cells

Delgado-Goñi, Teresa ; Galobart, Teresa Casals ; Wantuch, Slawomir ; Normantaite, Deimante ; Leach, Martin O. ; Whittaker, Steven R. ; Beloueche-Babari, Mounia

BRAF inhibitors, such as vemurafenib, have shown efficacy in BRAF-mutant melanoma treatment but acquired-resistance invariably develops. Unveiling the potential vulnerabilities associated with vemurafenib resistance could provide rational strategies for combinatorial treatment.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

Hu, Cong ; Pang, Bo ; Lin, Guangzhu ; Zhen, Yu ; Yi, Huanfa

In recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)

James, Andrew D. ; Richardson, Daniel A. ; Oh, In-Whan ; Sritangos, Pishyaporn ; Attard, Thomas ; Barrett, Lisa ; Bruce, Jason I. E.

Pancreatic ductal adenocarcinoma (PDAC) has poor survival and treatment options. PDAC cells shift their metabolism towards glycolysis, which fuels the plasma membrane calcium pump (PMCA), thereby preventing Ca2+-dependent cell death. The ATP-generating pyruvate kinase-M2 (PKM2) is oncogenic and overexpressed in PDAC. This study investigated the PKM2-derived ATP supply to the PMCA as a potential therapeutic locus.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer

Kawashima, Masahiro ; Tokiwa, Mariko ; Nishimura, Tomomi ; Kawata, Yukiko ; Sugimoto, Masahiro ; Kataoka, Tatsuki R. ; Sakurai, Takaki ; Iwaisako, Keiko ; Suzuki, Eiji ; Hagiwara, Masatoshi ; Harris, Adrian L. ; Toi, Masakazu

The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS).

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Reprogramming of fatty acid metabolism in cancer

Koundouros, Nikos ; Poulogiannis, George

A common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Protein kinase D1 regulates metabolic switch in pancreatic cancer via modulation of mTORC1

Kumari, Sonam ; Khan, Sheema ; Sekhri, Radhika ; Mandil, Hassan ; Behrman, Stephen ; Yallapu, Murali M. ; Chauhan, Subhash C. ; Jaggi, Meena

Protein kinase D1 (PKD1) is a serine–threonine kinase that regulates various functions within the cell. Herein, we report the significance of PKD1 expression in glucose metabolism resulting in pancreatic cancer (PanCa) progression and chemo-resistance.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention

Li, Bo ; Liao, Zhipeng ; Mo, Yingxi ; Zhao, Weilin ; Zhou, Xiaohui ; Xiao, Xiling ; Cui, Wanmeng ; Feng, Guofei ; Zhong, Suhua ; Liang, Yushan ; Du, Chunping ; Huang, Guangwu ; Li, Ping ; Xiao, Xue ; Zhou, Xiaoying ; Wang, Rensheng ; Zhang, Zhe

3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC).

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Activation of the reverse transsulfuration pathway through NRF2/CBS confers erastin-induced ferroptosis resistance

Liu, Nan ; Lin, Xiaoli ; Huang, Chengying

Ferroptosis is an iron-dependent, lipid peroxide-mediated cell death that may be exploited to selective elimination of damaged and malignant cells. Recent studies have identified that small-molecule erastin specifically inhibits transmembrane cystine–glutamate antiporter system xc−, prevents extracellular cystine import and ultimately causes ferroptosis in certain cancer cells. In this study, we aimed to investigate the molecular mechanism underlying erastin-induced ferroptosis resistance in [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin

Lord, Simon R. ; Collins, Jennifer M. ; Cheng, Wei-Chen ; Haider, Syed ; Wigfield, Simon ; Gaude, Edoardo ; Fielding, Barbara A. ; Pinnick, Katherine E. ; Harjes, Ulrike ; Segaran, Ashvina ; Jha, Pooja ; Hoefler, Gerald ; Pollak, Michael N. ; Thompson, Alastair M. ; Roy, Pankaj G. ; English, Ruth ; Adams, Rosie F. ; Frezza, Christian ; Buffa, Francesca M. ; Karpe, Fredrik ; Harris, Adrian L.

Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Targeting aerobic glycolysis by dichloroacetate improves Newcastle disease virus-mediated viro-immunotherapy in hepatocellular carcinoma

Meng, Gang ; Li, Binghua ; Chen, Anxian ; Zheng, Meihong ; Xu, Tiancheng ; Zhang, Hailin ; Dong, Jie ; Wu, Junhua ; Yu, Decai ; Wei, Jiwu

Oncolytic viro-immunotherapy holds promise for cancer treatment. While immune activation can be robustly triggered by oncolytic viruses, negative feedback is often upregulated in the tumour microenvironment (TME). Lactate accumulation, signal transducer and activator of transcription 3 (STAT3) activation, indoleamine 2,3-dioxygenase 1 (IDO1) expression, and myeloid-derived suppressor cell (MDSC) infiltration coordinate to shape the immunosuppressive TME.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

The therapeutic potential of targeting tryptophan catabolism in cancer

Opitz, Christiane A. ; Somarribas Patterson, Luis F. ; Mohapatra, Soumya R. ; Dewi, Dyah L. ; Sadik, Ahmed ; Platten, Michael ; Trump, Saskia

Based on its effects on both tumour cell intrinsic malignant properties as well as anti-tumour immune responses, tryptophan catabolism has emerged as an important metabolic regulator of cancer progression. Three enzymes, indoleamine-2,3-dioxygenase 1 and 2 (IDO1/2) and tryptophan-2,3-dioxygenase (TDO2), catalyse the first step of the degradation of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). The notion of inhibiting IDO1 using small-molecule inhibitors elicited high hopes of [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Oncogenic pathways and the electron transport chain: a dangeROS liaison

Raimondi, Vittoria ; Ciccarese, Francesco ; Ciminale, Vincenzo

Driver mutations in oncogenic pathways, rewiring of cellular metabolism and altered ROS homoeostasis are intimately connected hallmarks of cancer. Electrons derived from different metabolic processes are channelled into the mitochondrial electron transport chain (ETC) to fuel the oxidative phosphorylation process. Electrons leaking from the ETC can prematurely react with oxygen, resulting in the generation of reactive oxygen species (ROS). Several signalling pathways are affected by ROS, which [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Defining a metabolic landscape of tumours: genome meets metabolism

Seth Nanda, Chandan ; Venkateswaran, Sharavan Vishaan ; Patani, Neill ; Yuneva, Mariia

Cancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin

Sivalingam, Vanitha N. ; Latif, Ayşe ; Kitson, Sarah ; McVey, Rhona ; Finegan, Katherine G. ; Marshall, Kay ; Lisanti, Michael P. ; Sotgia, Federica ; Stratford, Ian J. ; Crosbie, Emma J.

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin’s anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Serotonin activates glycolysis and mitochondria biogenesis in human breast cancer cells through activation of the Jak1/STAT3/ERK1/2 and adenylate cyclase/PKA, respectively

Sola-Penna, Mauro ; Paixão, Larissa P. ; Branco, Jessica R. ; Ochioni, Alan C. ; Albanese, Jamille M. ; Mundim, Davi M. ; Baptista-de-Souza, Daniela ; Figueiredo, Claudia P. ; Coelho, Wagner S. ; Marcondes, Mariah C. ; Zancan, Patricia

Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Metabolic rewiring and redox alterations in malignant pleural mesothelioma

Urso, Loredana ; Cavallari, Ilaria ; Sharova, Evgeniya ; Ciccarese, Francesco ; Pasello, Giulia ; Ciminale, Vincenzo

Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

New aspects of amino acid metabolism in cancer

Vettore, Lisa ; Westbrook, Rebecca L. ; Tennant, Daniel A.

An abundant supply of amino acids is important for cancers to sustain their proliferative drive. Alongside their direct role as substrates for protein synthesis, they can have roles in energy generation, driving the synthesis of nucleosides and maintenance of cellular redox homoeostasis. As cancer cells exist within a complex and often nutrient-poor microenvironment, they sometimes exist as part of a metabolic community, forming relationships that can be both symbiotic and parasitic. Indeed, [...]

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

MFN1-dependent alteration of mitochondrial dynamics drives hepatocellular carcinoma metastasis by glucose metabolic reprogramming

Zhang, Ze ; Li, Tian-En ; Chen, Mo ; Xu, Da ; Zhu, Ying ; Hu, Bei-Yuan ; Lin, Zhi-Fei ; Pan, Jun-Jie ; Wang, Xuan ; Wu, Chao ; Zheng, Yan ; Lu, Lu ; Jia, Hu-Liang ; Gao, Song ; Dong, Qiong-Zhu ; Qin, Lun-Xiu

Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma

Zhang, Ze ; Liu, Ruoyan ; Shuai, Yanjie ; Huang, Yuting ; Jin, Rui ; Wang, Xudong ; Luo, Jingtao

Glutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Metabolism and cancer: the future is now

Frezza, Christian

In the last decade, the field of cancer metabolism transformed itself from being a description of the metabolic features of cancer cells to become a key component of cellular transformation. Now, the potential role of this field in cancer biology is ready to be unravelled.

Ce dossier présente une série d'articles concernant le métabolisme des cellules cancéreuses, notamment les processus métaboliques susceptibles de constituer des cibles thérapeutiques

Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

Harris, Adrian L.

Cancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical [...]