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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.
International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.
Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.
Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.
Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.
International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.
Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.
Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.
Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.
An International Open Access Journal Devoted to General Medicine.
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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM and Matrisian LM: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74:2913–2921. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG and Karamouzis MV: Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 12:173–181. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hu JX, Zhao CF, Chen WB, Liu QC, Li QW, Lin YY and Gao F: Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol. 27:4298–4321. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG and McCain RS: Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 24:4846–4861. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Picozzi VJ, Oh SY, Edwards A, Mandelson MT, Dorer R, Rocha FG, Alseidi A, Biehl T, Traverso LW, Helton WS and Kozarek RA: Five-year actual overall survival in resected pancreatic cancer: A contemporary single-institution experience from a multidisciplinary perspective. Ann Surg Oncol. 24:1722–1730. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 369:1691–1703. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, et al: FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 379:2395–2406. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Upadhrasta S and Zheng L: Strategies in developing immunotherapy for pancreatic cancer: Recognizing and correcting multiple immune 'defects' in the tumor microenvironment. J Clin Med. 8:14722019. View Article : Google Scholar | |
|
Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, et al: Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. 155:29–32. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
O'Hara M, O'Reilly E, Rosemarie M, Varadhachary G, Wainberg ZA, Ko A, Fisher GA, Rahma O, Lyman JP, Cabanski CR, et al: Abstract CT004: A phase Ib study of CD40 agonistic monoclonal antibody APX005M together with gemcitabine (Gem) and nab-paclitaxel (NP) with or without nivolumab (Nivo) in untreated metastatic ductal pancreatic adenocarcinoma (PDAC) patients. Cancer Res. 79(Suppl 13): CT0042019. View Article : Google Scholar | |
|
Bahary N, Garrido-Laguna I, Cinar P, O'Rourke MA, Somer BG, Nyak-Kapoor A, Lee JS, Munn D, Paul Kennedy E, Vahanian NN, et al: Phase 2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreas cancer: Interim analysis. J Clin Oncol. 34(Suppl 15): S30202016. View Article : Google Scholar | |
|
Di Federico A, Tateo V, Parisi C, Formica F, Carloni R, Frega G, Rizzo A, Ricci D, Di Marco M, Palloni A and Brandi G: Hacking pancreatic cancer: Present and future of personalized medicine. Pharmaceuticals (Basel). 14:6772021. View Article : Google Scholar | |
|
Yang Y, Liu H, Li Z, Zhao Z, Yip-Schneider M, Fan Q, Schmidt CM, Chiorean EG, Xie J, Cheng L, et al: Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers. Int J Biochem Mol Biol. 2:89–98. 2011.PubMed/NCBI | |
|
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, et al: Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 514:628–632. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu M, Liu W, Qin Y, Xu X, Yu X, Zhuo Q and Ji S: Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer. Exp Hematol Oncol. 9:232020. View Article : Google Scholar | |
|
Daemen A, Peterson D, Sahu N, McCord R, Du X, Liu B, Kowanetz K, Hong R, Moffat J, Gao M, et al: Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors. Proc Natl Acad Sci USA. 112:E4410–E4417. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Karasinska JM, Topham JT, Kalloger SE, Jang GH, Denroche RE, Culibrk L, Williamson LM, Wong HL, Lee MK, O'Kane GM, et al: Altered gene expression along the glycolysis-cholesterol synthesis axis is associated with outcome in pancreatic cancer. Clin Cancer Res. 26:135–146. 2020. View Article : Google Scholar | |
|
Halbrook CJ and Lyssiotis CA: Employing metabolism to improve the diagnosis and treatment of pancreatic cancer. Cancer Cell. 31:5–19. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Perusina Lanfranca M, Thompson JK, Bednar F, Halbrook C, Lyssiotis C, Levi B and Frankel TL: Metabolism and epigenetics of pancreatic cancer stem cells. Semin Cancer Biol. 57:19–26. 2019. View Article : Google Scholar : | |
|
Perera RM and Bardeesy N: Pancreatic cancer metabolism: Breaking it down to build it back up. Cancer Discov. 5:1247–1261. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Dal Molin M, Zhang M, De Wilde RF, Ottenhof NA, Rezaee N, Wolfgang CL, Blackford A, Vogelstein B, Kinzler KW, Papadopoulos N, et al: Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: Results of whole-exome sequencing analysis. Clin Cancer Res. 21:1944–1950. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, Cooc J, Weinkle J, Kim GE, Jakkula L, et al: Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 17:500–503. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, Rashid NU, Williams LA, Eaton SC, Chung AH, et al: Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 47:1168–1178. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L, Zhao H and Yan H: Gene expression profiling of 1200 pancreatic ductal adenocarcinoma reveals novel subtypes. BMC Cancer. 18:6032018. View Article : Google Scholar : PubMed/NCBI | |
|
Maurer C, Holmstrom SR, He J, Laise P, Su T, Ahmed A, Hibshoosh H, Chabot JA, Oberstein PE, Sepulveda AR, et al: Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes. Gut. 68:1034–1043. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Chan-Seng-Yue M, Kim JC, Wilson GW, Ng K, Figueroa EF, O'Kane GM, Connor AA, Denroche RE, Grant RC, McLeod J, et al: Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution. Nat Genet. 52:231–240. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lonardo E, Frias-Aldeguer J, Hermann PC and Heeschen C: Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle. 11:1282–1290. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Richards KE, Zeleniak AE, Fishel ML, Wu J, Littlepage LE and Hill R: Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene. 36:1770–1778. 2017. View Article : Google Scholar : | |
|
Mejia I, Bodapati S, Chen KT and Díaz B: Pancreatic adenocarcinoma invasiveness and the tumor microenvironment: From biology to clinical trials. Biomedicines. 8:4012020. View Article : Google Scholar : | |
|
Sherman MH, Yu RT, Tseng TW, Sousa CM, Liu S, Truitt ML, He N, Ding N, Liddle C, Atkins AR, et al: Stromal cues regulate the pancreatic cancer epigenome and metabolome. Proc Natl Acad Sci USA. 114:1129–1134. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H, et al: Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 536:479–483. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA and Jørgensen C: Oncogenic KRAS regulates tumor cell signaling via stromal reciprocation. Cell. 165:910–920. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Juiz N, Elkaoutari A, Bigonnet M, Gayet O, Roques J, Nicolle R, Iovanna J and Dusetti N: Basal-like and classical cells coexistence in pancreatic cancer revealed by single cell analysis. bioRxiv. 2020. | |
|
Suzuki T, Otsuka M, Seimiya T, Iwata T, Kishikawa T and Koike K: The biological role of metabolic reprogramming in pancreatic cancer. MedComm (2020). 1:302–310. 2020. | |
|
Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV and Smans K: Lipogenesis and lipolysis: The pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res. 52:585–589. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Sancho P, Burgos-Ramos E, Tavera A, Bou Kheir T, Jagust P, Schoenhals M, Barneda D, Sellers K, Campos-Olivas R, Graña O, et al: MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metab. 22:590–605. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Kamphorst JJ, Nofal M, Commisso C, Hackett SR, Lu W, Grabocka E, Vander Heiden MG, Miller G, Drebin JA, Bar-Sagi D, et al: Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 75:544–553. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshida GJ: Metabolic reprogramming: The emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 34:1112015. View Article : Google Scholar : PubMed/NCBI | |
|
Yu M, Zhou Q, Zhou Y, Fu Z, Tan L, Ye X, Zeng B, Gao W, Zhou J, Liu Y, et al: Metabolic phenotypes in pancreatic cancer. PLoS One. 10:e01151532015. View Article : Google Scholar : PubMed/NCBI | |
|
Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N, et al: Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun. 9:19782018. View Article : Google Scholar : PubMed/NCBI | |
|
Kaoutari AE, Fraunhoffer NA, Hoare O, Teyssedou C, Soubeyran P, Gayet O, Roques J, Lomberk G, Urrutia R, Dusetti N and Iovanna J: Metabolomic profiling of pancreatic adenocarcinoma reveals key features driving clinical outcome and drug resistance. EBioMedicine. 66:1033322021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Q, Ge W, Wang T, Lan J, Martínez-Jarquín S, Wolfrum C, Stoffel M and Zenobi R: High-throughput single-cell mass spectrometry reveals abnormal lipid metabolism in pancreatic ductal adenocarcinoma. Angew Chem Int Ed Engl. 60:24534–24542. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Argüello RJ, Combes AJ, Char R, Gigan JP, Baaziz AI, Bousiquot E, Camosseto V, Samad B, Tsui J, Yan P, et al: SCENITH: A flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab. 32:1063–1075.e7. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Miller A, Nagy C, Knapp B, Laengle J, Ponweiser E, Groeger M, Starkl P, Bergmann M, Wagner O and Haschemi A: Exploring metabolic configurations of single cells within complex tissue microenvironments. Cell Metab. 26:788–800.e6. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ambrosini G, Dalla Pozza E, Fanelli G, Di Carlo C, Vettori A, Cannino G, Cavallini C, Carmona-Carmona CA, Brandi J, Rinalducci S, et al: Progressively de-differentiated pancreatic cancer cells shift from glycolysis to oxidative metabolism and gain a quiescent stem state. Cells. 9:15722020. View Article : Google Scholar : | |
|
Biancur DE, Paulo JA, Małachowska B, Quiles Del Rey M, Sousa CM, Wang X, Sohn ASW, Chu GC, Gygi SP, Harper JW, et al: Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism. Nat Commun. 8:159652017. View Article : Google Scholar : PubMed/NCBI | |
|
Koppenol WH, Bounds PL and Dang CV: Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 11:325–337. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Liu XS, Little JB and Yuan ZM: Glycolytic metabolism influences global chromatin structure. Oncotarget. 6:4214–4225. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Liberti MV and Locasale JW: The Warburg effect: How does it benefit cancer cells? Trends Biochem Sci. 41:211–218. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Husain Z, Huang Y, Seth P and Sukhatme VP: Tumor-derived lactate modifies antitumor immune response: Effect on myeloid-derived suppressor cells and NK cells. J Immunol. 191:1486–1495. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Du J, Gu J, Deng J, Kong L, Guo Y, Jin C, Bao Y, Fu D and Li J: The expression and survival significance of glucose transporter-1 in pancreatic cancer: Meta-analysis, bioinformatics analysis and retrospective study. Cancer Invest. 39:741–755. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Lee EE, Ma J, Sacharidou A, Mi W, Salato VK, Nguyen N, Jiang Y, Pascual JM, North PE, Shaul PW, et al: A protein kinase C phosphorylation motif in GLUT1 affects glucose transport and is mutated in GLUT1 deficiency syndrome. Mol Cell. 58:845–853. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng CS, Tan HY, Wang N, Chen L, Meng Z, Chen Z and Feng Y: Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression. Clin Transl Med. 11:e4672021. View Article : Google Scholar : PubMed/NCBI | |
|
Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, et al: Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 149:656–670. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang W, Qiao L, Zuo D, Qin D, Xiao J, An H, Wang Y, Zhang X, Jin Y and Ren L: Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer. Ann Transl Med. 9:3582021. View Article : Google Scholar : PubMed/NCBI | |
|
Yalcin A, Solakoglu TH, Ozcan SC, Guzel S, Peker S, Celikler S, Balaban BD, Sevinc E, Gurpinar Y and Chesney JA: 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro. Biochem Biophys Res Commun. 484:687–693. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ji S, Zhang B, Liu J, Qin Y, Liang C, Shi S, Jin K, Liang D, Xu W, Xu H, et al: ALDOA functions as an oncogene in the highly metastatic pancreatic cancer. Cancer Lett. 374:127–135. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Principe M, Borgoni S, Cascione M, Chattaragada MS, Ferri-Borgogno S, Capello M, Bulfamante S, Chapelle J, Di Modugno F, Defilippi P, et al: Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis. J Hematol Oncol. 10:162017. View Article : Google Scholar : PubMed/NCBI | |
|
Principe M, Ceruti P, Shih NY, Chattaragada MS, Rolla S, Conti L, Bestagno M, Zentilin L, Yang SH, Migliorini P, et al: Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells. Oncotarget. 6:11098–11113. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T and Seufferlein T: PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 15:32016. View Article : Google Scholar | |
|
Thews O and Riemann A: Tumor pH and metastasis: A malignant process beyond hypoxia. Cancer Metastasis Rev. 38:113–129. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezène P, Dusetti NJ, Loncle C, Calvo E, Turrini O, et al: Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 110:3919–3924. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN and Halestrap AP: CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 19:3896–3904. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Semenza GL: Tumor metabolism: Cancer cells give and take lactate. J Clin Invest. 118:3835–3837. 2008.PubMed/NCBI | |
|
Sun X, Wang M, Wang M, Yao L, Li X, Dong H, Li M, Sun T, Liu X, Liu Y and Xu Y: Role of proton-coupled monocarboxylate transporters in cancer: From metabolic crosstalk to therapeutic potential. Front cell Dev Biol. 8:6512020. View Article : Google Scholar : PubMed/NCBI | |
|
Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, et al: The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 8:3984–4001. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Benny S, Mishra R, Manojkumar MK and Aneesh TP: From Warburg effect to reverse Warburg effect; the new horizons of anti-cancer therapy. Med Hypotheses. 144:1102162020. View Article : Google Scholar : PubMed/NCBI | |
|
Roland CL, Arumugam T, Deng D, Liu SH, Philip B, Gomez S, Burns WR, Ramachandran V, Wang H, Cruz-Monserrate Z and Logsdon CD: Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res. 74:5301–5310. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Benton CR, Yoshida Y, Lally J, Han X-X, Hatta H and Bonen A: PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol Genomics. 35:45–54. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng CF, Ku HC and Lin H: PGC-1α as a pivotal factor in lipid and metabolic regulation. Int J Mol Sci. 19:34472018. View Article : Google Scholar | |
|
Schneiderhan W, Scheler M, Holzmann KH, Marx M, Gschwend JE, Bucholz M, Gress TM, Seufferlein T, Adler G and Oswald F: CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models. Gut. 58:1391–1398. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Hwang HK, Lee WJ and Kang CM: MCT4 as a potential therapeutic target to augment gemcitabine chemosensitivity in resected pancreatic cancer. Cell Oncol (Dordr). 44:1363–1371. 2021. View Article : Google Scholar | |
|
Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA and Hall MN: Dual inhibition of the lactate transporters MCT1 and MCT4 Is synthetic lethal with metformin due to NAD+ depletion in cancer cells. Cell Rep. 25:3047–3058.e4. 2018. View Article : Google Scholar | |
|
Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, et al: Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 118:3930–3942. 2008.PubMed/NCBI | |
|
Wu DH, Liang H, Lu SN, Wang H, Su ZL, Zhang L, Ma JQ, Guo M, Tai S and Yu S: miR-124 suppresses pancreatic ductal adenocarcinoma growth by regulating monocarboxylate transporter 1-mediated cancer lactate metabolism. Cell Physiol Biochem. 50:924–935. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Lau AN, Li Z, Danai LV, Westermark AM, Darnell AM, Ferreira R, Gocheva V, Sivanand S, Lien EC, Sapp KM, et al: Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma. Elife. 9:e567822020. View Article : Google Scholar : PubMed/NCBI | |
|
Koundouros N and Poulogiannis G: Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 122:4–22. 2020. View Article : Google Scholar : | |
|
Alo PL, Amini M, Piro F, Pizzuti L, Sebastiani V, Botti C, Murari R, Zotti G and Di Tondo U: Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma. Anticancer Res. 27:2523–2527. 2007.PubMed/NCBI | |
|
Li N, Lu H, Chen C, Bu X and Huang P: Loss of fatty acid synthase inhibits the 'hER2-PI3K/Akt axis' activity and malignant phenotype of Caco-2 cells. Lipids Health Dis. 12:832013. View Article : Google Scholar | |
|
Menendez JA, Decker JP and Lupu R: In support of fatty acid synthase (FAS) as a metabolic oncogene: Extracellular acidosis acts in an epigenetic fashion activating FAS gene expression in cancer cells. J Cell Biochem. 94:1–4. 2005. View Article : Google Scholar | |
|
Shetty A, Nagesh PKB, Setua S, Hafeez BB, Jaggi M, Yallapu MM and Chauhan SC: Novel paclitaxel nanoformulation impairs de novo lipid synthesis in pancreatic cancer cells and enhances gemcitabine efficacy. ACS Omega. 5:8982–8991. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Tracz-Gaszewska Z and Dobrzyn P: Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers (Basel). 11:9482019. View Article : Google Scholar | |
|
Rysman E, Brusselmans K, Scheys K, Timmermans L, Derua R, Munck S, Van Veldhoven PP, Waltregny D, Daniëls VW, Machiels J, et al: De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res. 70:8117–8126. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Fritz V, Benfodda Z, Rodier G, Henriquet C, Iborra F, Avancès C, Allory Y, de la Taille A, Culine S, Blancou H, et al: Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol Cancer Ther. 9:1740–1754. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Eser S, Schnieke A, Schneider G and Saur D: Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer. 111:817–822. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Menendez JA: Fine-tuning the lipogenic/lipolytic balance to optimize the metabolic requirements of cancer cell growth: Molecular mechanisms and therapeutic perspectives. Biochim Biophys Acta. 1801:381–391. 2010. View Article : Google Scholar | |
|
Xu M, Jung X, Hines OJ, Eibl G and Chen Y: Obesity and pancreatic cancer: Overview of epidemiology and potential prevention by weight loss. Pancreas. 47:158–162. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML and Abbruzzese JL: Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA. 301:2553–2562. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Kasenda B, Bass A, Koeberle D, Pestalozzi B, Borner M, Herrmann R, Jost L, Lohri A and Hess V: Survival in overweight patients with advanced pancreatic carcinoma: A multicentre cohort study. BMC Cancer. 14:7282014. View Article : Google Scholar : PubMed/NCBI | |
|
Anderson AS, Renehan AG, Saxton JM, Bell J, Cade J, Cross AJ, King A, Riboli E, Sniehotta F, Treweek S, et al: Cancer prevention through weight control-where are we in 2020? Br J Cancer. 124:1049–1056. 2021. View Article : Google Scholar | |
|
Jacobs EJ, Newton CC, Patel AV, Stevens VL, Islami F, Flanders WD and Gapstur SM: The association between body mass index and pancreatic cancer: Variation by age at body mass index assessment. Am J Epidemiol. 189:108–115. 2020. View Article : Google Scholar | |
|
Chimento A, Casaburi I, Avena P, Trotta F, De Luca A, Rago V, Pezzi V and Sirianni R: Cholesterol and its metabolites in tumor growth: Therapeutic potential of statins in cancer treatment. Front Endocrinol (Lausanne). 9:8072019. View Article : Google Scholar | |
|
Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, Lac S, Borge L, Roques J, Gayet O, et al: Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 112:2473–2478. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Nam GH, Kwon M, Jung H, Ko E, Kim SA, Choi Y, Song SJ, Kim S, Lee Y, Kim GB, et al: Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer. J Immunother cancer. 9:e0024742021. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang W, Hu JW, He XR, Jin WL and He XY: Statins: A repurposed drug to fight cancer. J Exp Clin Cancer Res. 40:2412021. View Article : Google Scholar : PubMed/NCBI | |
|
Osmak M: Statins and cancer: Current and future prospects. Cancer Lett. 324:1–12. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y and Matsuzawa Y: Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer. 84:886–891. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Lersch C, Schmelz R, Erdmann J, Hollweck R, Schulte-Frohlinde E, Eckel F, Nader M and Schusdziarra V: Treatment of HCC with pravastatin, octreotide, or gemcitabine-a critical evaluation. Hepatogastroenterology. 51:1099–1103. 2004.PubMed/NCBI | |
|
Butera A, Roy M, Zampieri C, Mammarella E, Panatta E, Melino G, D'Alessandro A and Amelio I: p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer. Biol Direct. 17:62022. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Jin H, Guo X, Yang Z, Zhao L, Tang S, Mo P, Wu K, Nie Y, Pan Y and Fan D: Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by (1)H nuclear magnetic resonance-based metabonomic profiles. Clin Biochem. 45:1064–1069. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Urayama S, Zou W, Brooks K and Tolstikov V: Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom. 24:613–620. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wang G, Yao H, Gong Y, Lu Z, Pang R, Li Y, Yung Y, Song H, Liu J, Jin Y, et al: Metabolic detection and systems analyses of pancreatic ductal adenocarcinoma through machine learning, lipidomics, and multi-omics. Sci Adv. 7:eabh27242021. View Article : Google Scholar : PubMed/NCBI | |
|
Fang F, He X, Deng H, Chen Q, Lu J, Spraul M and Yu Y: Discrimination of metabolic profiles of pancreatic cancer from chronic pancreatitis by high-resolution magic angle spinning 1H nuclear magnetic resonance and principal components analysis. Cancer Sci. 98:1678–1682. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Liu F, Fan N, Zhou C, Li D, Macvicar T, Dong Q, Bruns CJ and Zhao Y: Targeting glutaminolysis: New perspectives to understand cancer development and novel strategies for potential target therapies. Front Oncol. 10:5895082020. View Article : Google Scholar : PubMed/NCBI | |
|
DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S and Thompson CB: Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA. 104:19345–19350. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Ghanem N, El-Baba C, Araji K, El-Khoury R, Usta J and Darwiche N: The pentose phosphate pathway in cancer: Regulation and therapeutic opportunities. Chemotherapy. 66:179–191. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ju HQ, Lin JF, Tian T, Xie D and Xu RH: NADPH homeostasis in cancer: Functions, mechanisms and therapeutic implications. Signal Transduct Target Ther. 5:2312020. View Article : Google Scholar : PubMed/NCBI | |
|
Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, et al: Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science. 368:85–89. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA and Thompson CB: ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 8:311–321. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Akella NM, Ciraku L and Reginato MJ: Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol. 17:522019. View Article : Google Scholar : PubMed/NCBI | |
|
Tong X, Zhao F and Thompson CB: The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Curr Opin Genet Dev. 19:32–37. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Bai C, Ruan Y, Liu M, Chu Q, Qiu L, Yang C and Li B: Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia. Nat Commun. 10:2012019. View Article : Google Scholar : PubMed/NCBI | |
|
Bott AJ, Shen J, Tonelli C, Zhan L, Sivaram N, Jiang YP, Yu X, Bhatt V, Chiles E, Zhong H, et al: Glutamine anabolism plays a critical role in pancreatic cancer by coupling carbon and nitrogen metabolism. Cell Rep. 29:1287–1298.e6. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Li T and Le A: Glutamine metabolism in cancer. The Heterogeneity of Cancer Metabolism. Le A: Springer International Publishing; Cham: pp. 13–32. 2018, View Article : Google Scholar | |
|
Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, et al: Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 496:101–105. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Li W, Chen C, Zhao X, Ye H, Zhao Y, Fu Z, Pan W, Zheng S, Wei L, Nong T, et al: HIF-2α regulates non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma. J Cell Mol Med. 21:2896–2908. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Raho S, Capobianco L, Malivindi R, Vozza A, Piazzolla C, De Leonardis F, Gorgoglione R, Scarcia P, Pezzuto F, Agrimi G, et al: KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth. Nat Metab. 2:1373–1381. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yang S, Hwang S, Kim M, Seo SB, Lee JH and Jeong SM: Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth through senescence inhibition. Cell Death Dis. 9:552018. View Article : Google Scholar : PubMed/NCBI | |
|
Wise DR, Deberardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB and Thompson CB: Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA. 105:18782–18787. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 458:762–765. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Roux C, Riganti C, Borgogno SF, Curto R, Curcio C, Catanzaro V, Digilio G, Padovan S, Puccinelli MP, Isabello M, et al: Endogenous glutamine decrease is associated with pancreatic cancer progression. Oncotarget. 8:95361–95376. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
He J, Li F, Zhou Y, Hou X, Liu S, Li X, Zhang Y, Jing X and Yang L: LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc. Cancer Lett. 469:419–428. 2020. View Article : Google Scholar | |
|
Lowman XH, Hanse EA, Yang Y, Ishak Gabra MB, Tran TQ, Li H and Kong M: p53 Promotes cancer cell adaptation to glutamine deprivation by upregulating Slc7a3 to increase arginine uptake. Cell Rep. 26:3051–3060.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Tajan M, Hock AK, Blagih J, Robertson NA, Labuschagne CF, Kruiswijk F, Humpton TJ, Adams PD and Vousden KH: A role for p53 in the adaptation to glutamine starvation through the expression of SLC1A3. Cell Metab. 28:721–736.e6. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Tran TQ, Lowman XH, Reid MA, Mendez-Dorantes C, Pan M, Yang Y and Kong M: Tumor-associated mutant p53 promotes cancer cell survival upon glutamine deprivation through p21 induction. Oncogene. 36:1991–2001. 2017. View Article : Google Scholar : | |
|
Dey P, Baddour J, Muller F, Wu CC, Wang H, Liao WT, Lan Z, Chen A, Gutschner T, Kang Y, et al: Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature. 542:119–123. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dai Z, Ramesh V and Locasale JW: The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet. 21:737–753. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wang G and Han JJ: Connections between metabolism and epigenetic modifications in cancer. Med Rev. 1:199–221. 2021. View Article : Google Scholar | |
|
Etchegaray JP and Mostoslavsky R: Interplay between metabolism and epigenetics: A nuclear adaptation to environmental changes. Mol Cell. 62:695–711. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H, Nagle JM, Boukhali M, Hayward MC, Li YY, Chen T, et al: LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature. 539:390–395. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Li QF, Chow H, Choi S and Leung YC: Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of snail, slug, twist, and MMP1/9. J Physiol Biochem. 76:73–83. 2020. View Article : Google Scholar | |
|
Wang J, Yang S, He P, Schetter AJ, Gaedcke J, Ghadimi BM, Ried T, Yfantis HG, Lee DH, Gaida MM, et al: Endothelial nitric oxide synthase traffic inducer (NOSTRIN) is a negative regulator of disease aggressiveness in pancreatic cancer. Clin Cancer Res. 22:5992–6001. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Herner A, Sauliunaite D, Michalski CW, Erkan M, De Oliveira T, Abiatari I, Kong B, Esposito I, Friess H and Kleeff J: Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras-MAPK signaling. Int J Cancer. 129:2349–2359. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Gitto SB, Pandey V, Oyer JL, Copik AJ, Hogan FC, Phanstiel O IV and Altomare DA: Difluoromethylornithine combined with a polyamine transport inhibitor is effective against gemcitabine resistant pancreatic cancer. Mol Pharm. 15:369–376. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kremer JC, Prudner BC, Lange SES, Bean GR, Schultze MB, Brashears CB, Radyk MD, Redlich N, Tzeng SC, Kami K, et al: Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Rep. 18:991–1004. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Davidson SM, Jonas O, Keibler MA, Hou HW, Luengo A, Mayers JR, Wyckoff J, Del Rosario AM, Whitman M, Chin CR, et al: Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat Med. 23:235–241. 2017. View Article : Google Scholar | |
|
Maertin S, Elperin JM, Lotshaw E, Sendler M, Speakman SD, Takakura K, Reicher BM, Mareninova OA, Grippo PJ, Mayerle J, et al: Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges. Am J Physiol Gastrointest Liver Physiol. 313:G524–G536. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Saliakoura M, Sebastiano MR, Nikdima I, Pozzato C and Konstantinidou G: Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy. J Exp Clin Cancer Res. 41:162022. View Article : Google Scholar : PubMed/NCBI | |
|
Piffoux M, Eriau E and Cassier PA: Autophagy as a therapeutic target in pancreatic cancer. Br J Cancer. 124:333–344. 2021. View Article : Google Scholar : | |
|
Li J, Chen X, Kang R, Zeh H, Klionsky DJ and Tang D: Regulation and function of autophagy in pancreatic cancer. Autophagy. 17:3275–3296. 2021. View Article : Google Scholar : | |
|
Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, et al: Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 581:100–105. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Mukhopadhyay S, Biancur DE, Parker SJ, Yamamoto K, Banh RS, Paulo JA, Mancias JD and Kimmelman AC: Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11. Proc Natl Acad Sci USA. 118:e20214751182021. View Article : Google Scholar : PubMed/NCBI | |
|
Ashton TM, Gillies McKenna W, Kunz-Schughart LA and Higgins GS: Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 24:2482–2490. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zong WX, Rabinowitz JD and White E: Mitochondria and cancer. Mol Cell. 61:667–676. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Lambert A and Brand M: Reactive oxygen species production by mitochondria. Methods Mol Biol. 554:165–181. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR and Chandel NS: Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA. 107:8788–8793. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Nevala-Plagemann C, Hidalgo M and Garrido-Laguna I: From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. Nat Rev Clin Oncol. 17:108–123. 2020. View Article : Google Scholar | |
|
Masoud R, Reyes-Castellanos G, Lac S, Garcia J, Dou S, Shintu L, Abdel Hadi N, Gicquel T, El Kaoutari A, Diémé B, et al: Targeting mitochondrial complex I overcomes chemoresistance in high OXPHOS pancreatic cancer. Cell Rep Med. 1:1001432020. View Article : Google Scholar : PubMed/NCBI | |
|
Candido S, Abrams SL, Steelman L, Lertpiriyapong K, Martelli AM, Cocco L, Ratti S, Follo MY, Murata RM, Rosalen PL, et al: Metformin influences drug sensitivity in pancreatic cancer cells. Adv Biol Regul. 68:13–30. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zannella VE, Dal Pra A, Muaddi H, McKee TD, Stapleton S, Sykes J, Glicksman R, Chaib S, Zamiara P, Milosevic M, et al: Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response. Clin Cancer Res. 19:6741–6750. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Neesse A, Bauer CA, Öhlund D, Lauth M, Buchholz M, Michl P, Tuveson DA and Gress TM: Stromal biology and therapy in pancreatic cancer: Ready for clinical translation? Gut. 68:159–171. 2019. View Article : Google Scholar | |
|
Croucher DR, Saunders DN, Lobov S and Ranson M: Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev Cancer. 8:535–545. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Harris NLE, Vennin C, Conway JRW, Vine KL, Pinese M, Cowley MJ, Shearer RF, Lucas MC, Herrmann D, Allam AH, et al: SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene. 36:4288–4298. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang B, Zhou L, Lu J, Wang Y, Liu C, You L and Guo J: Stroma-targeting therapy in pancreatic cancer: One coin with two sides? Front Oncol. 10:5763992020. View Article : Google Scholar : PubMed/NCBI | |
|
Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, Dekleva EN, Saunders T, Becerra CP, Tattersall IW, et al: Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 25:735–747. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
de la Fouchardière C, Gamradt P, Chabaud S, Raddaz M, Blanc E, Msika O, Treilleux I, Bachy S, Cattey-Javouhey A, Guibert P, et al: A promising biomarker and therapeutic target in patients with advanced PDAC: The stromal protein βig-h3. J Pers Med. 12:6232022. View Article : Google Scholar | |
|
Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, et al: Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 324:1457–1461. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Bulle A and Lim KH: Beyond just a tight fortress: Contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer. Signal Transduct Target Ther. 5:2492020. View Article : Google Scholar : PubMed/NCBI | |
|
Malchiodi ZX, Cao H, Gay MD, Safronenka A, Bansal S, Tucker RD, Weinberg BA, Cheema A, Shivapurkar N and Smith JP: Cholecystokinin receptor antagonist improves efficacy of chemotherapy in murine models of pancreatic cancer by altering the tumor microenvironment. Cancers (Basel). 13:49492021. View Article : Google Scholar | |
|
Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, Fitamant J, Jones PD, Ghanta KS, Kawano S, et al: Stromal response to hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci USA. 111:E3091–E3100. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Y, Zhang C, Jiang K, Werner J, Bazhin AV and D'Haese JG: The role of stellate cells in pancreatic ductal adenocarcinoma: Targeting perspectives. Front Oncol. 10:6219372021. View Article : Google Scholar : PubMed/NCBI | |
|
Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A and Sotgia F: Understanding the 'lethal' drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther. 10:537–542. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP and Martinez-Outschoorn UE: Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: Implications for preventing chemotherapy resistance. Cancer Biol Ther. 12:1085–1097. 2011. View Article : Google Scholar | |
|
Mariño G and Kroemer G: Ammonia: A diffusible factor released by proliferating cells that induces autophagy. Sci Signal. 3:pe192010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al: Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 5:e102502016. View Article : Google Scholar : PubMed/NCBI | |
|
Waldenmaier M, Seibold T, Seufferlein T and Eiseler T: Pancreatic cancer small extracellular vesicles (exosomes): A tale of short- and long-distance communication. Cancers (Basel). 13:48442021. View Article : Google Scholar | |
|
Takikawa T, Masamune A, Yoshida N, Hamada S, Kogure T and Shimosegawa T: Exosomes derived from pancreatic stellate cells: MicroRNA signature and effects on pancreatic cancer cells. Pancreas. 46:19–27. 2017. View Article : Google Scholar | |
|
Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS and DeBerardinis RJ: Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 481:385–388. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T, Borge L, Lac S, Roques J, Lavaut MN, Berthezène P, et al: Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun. 8:160312017. View Article : Google Scholar : PubMed/NCBI | |
|
Begum A, McMillan RH, Chang YT, Penchev VR, Rajeshkumar NV, Maitra A, Goggins MG, Eshelman JR, Wolfgang CL, Rasheed ZA and Matsui W: Direct interactions with cancer-associated fibroblasts lead to enhanced pancreatic cancer stem cell function. Pancreas. 48:329–334. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Cai Z, Liang Y, Xing C, Wang H, Hu P, Li J, Huang H, Wang W and Jiang C: Cancer-associated adipocytes exhibit distinct phenotypes and facilitate tumor progression in pancreatic cancer. Oncol Rep. 42:2537–2549. 2019.PubMed/NCBI | |
|
Meyer KA, Neeley CK, Baker NA, Washabaugh AR, Flesher CG, Nelson BS, Frankel TL, Lumeng CN, Lyssiotis CA, Wynn ML, et al: Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer. Biochem Biophys Rep. 7:144–149. 2016.PubMed/NCBI | |
|
Ye H, Zhou Q, Zheng S, Li G, Lin Q, Wei L, Fu Z, Zhang B, Liu Y, Li Z and Chen R: Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma. Cell Death Dis. 9:4532018. View Article : Google Scholar : PubMed/NCBI | |
|
Asencio-Barría C, Defamie N, Sáez JC, Mesnil M and Godoy AS: Direct intercellular communications and cancer: A snapshot of the biological roles of connexins in prostate cancer. Cancers (Basel). 11:13702019. View Article : Google Scholar | |
|
Luo M, Luo Y, Mao N, Huang G, Teng C, Wang H, Wu J, Liao X and Yang J: Cancer-associated fibroblasts accelerate malignant progression of non-small cell lung cancer via connexin 43-formed unidirectional gap junctional intercellular communication. Cell Physiol Biochem. 51:315–336. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Liu X, Qiu Y, Shi Y, Cai J, Wang B, Wei X, Ke Q, Sui X, Wang Y, et al: Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells. J Hematol Oncol. 11:112018. View Article : Google Scholar : PubMed/NCBI | |
|
Marlein CR, Piddock RE, Mistry JJ, Zaitseva L, Hellmich C, Horton RH, Zhou Z, Auger MJ, Bowles KM and Rushworth SA: CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Res. 79:2285–2297. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Dovmark TH, Saccomano M, Hulikova A, Alves F and Swietach P: Connexin-43 channels are a pathway for discharging lactate from glycolytic pancreatic ductal adenocarcinoma cells. Oncogene. 36:4538–4550. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Yu Z, Pestell TG, Lisanti MP and Pestell RG: Cancer stem cells. Int J Biochem Cell Biol. 44:2144–2151. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Mummery CL, van de Stolpe A, Roelen B and Clevers H: Chapter 12-Cancer stem cells: Where do they come from and where are they going? Stem Cells. 3rd. Mummery CL, van de Stolpe A, Roelen B and Clevers HB: Academic Press; Boston: pp. 299–328. 2021, View Article : Google Scholar | |
|
Nguyen LV, Vanner R, Dirks P and Eaves CJ: Cancer stem cells: An evolving concept. Nat Rev Cancer. 12:133–143. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF and Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res. 67:1030–1038. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D and Szylberg Ł: Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep. 46:6629–6645. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ and Heeschen C: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 1:313–323. 2007. View Article : Google Scholar | |
|
Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, et al: Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst. 102:340–351. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li C, Wu JJ, Hynes M, Dosch J, Sarkar B, Welling TH, Pasca di Magliano M and Simeone DM: c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology. 141:2218–2227.e5. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Miranda-Lorenzo I, Dorado J, Lonardo E, Alcala S, Serrano AG, Clausell-Tormos J, Cioffi M, Megias D, Zagorac S, Balic A, et al: Intracellular autofluorescence: A biomarker for epithelial cancer stem cells. Nat Methods. 11:1161–1169. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sancho P, Alcala S, Usachov V, Hermann PC and Sainz B Jr: The ever-changing landscape of pancreatic cancer stem cells. Pancreatology. 16:489–496. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Depeint F, Bruce WR, Shangari N, Mehta R and O'Brien PJ: Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 163:94–112. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP and Leach SD: Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci USA. 107:75–80. 2010. View Article : Google Scholar : | |
|
Sainz BJ Jr, Alcala S, Garcia E, Sanchez-Ripoll Y, Azevedo MM, Cioffi M, Tatari M, Miranda-Lorenzo I, Hidalgo M, Gomez-Lopez G, et al: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut. 64:1921–1935. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sainz B Jr, Martín B, Tatari M, Heeschen C and Guerra S: ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 74:7309–7320. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rausch V, Liu L, Apel A, Rettig T, Gladkich J, Labsch S, Kallifatidis G, Kaczorowski A, Groth A, Gross W, et al: Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment. J Pathol. 227:325–335. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu H, Wang D, Zhang L, Xie X, Wu Y, Liu Y, Shao G and Su Z: Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncol Rep. 32:935–942. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jagust P, Alcalá S, Sainz B Jr, Heeschen C and Sancho P: Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells. World J Stem Cells. 12:1410–1428. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Li D, Fu Z, Chen R, Zhao X, Zhou Y, Zeng B, Yu M, Zhou Q, Lin Q, Gao W, et al: Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy. Oncotarget. 6:31151–31163. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Brandi J, Dando I, Pozza ED, Biondani G, Jenkins R, Elliott V, Park K, Fanelli G, Zolla L, Costello E, et al: Proteomic analysis of pancreatic cancer stem cells: Functional role of fatty acid synthesis and mevalonate pathways. J Proteomics. 150:310–322. 2017. View Article : Google Scholar | |
|
McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, et al: Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat Genet. 49:367–376. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Alcalá S, Sancho P, Martinelli P, Navarro D, Pedrero C, Martín-Hijano L, Valle S, Earl J, Rodríguez-Serrano M, Ruiz-Cañas L, et al: ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity. Nat Commun. 11:26822020. View Article : Google Scholar : PubMed/NCBI | |
|
Nimmakayala RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, et al: Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene. 40:215–231. 2021. View Article : Google Scholar | |
|
Alistar A, Morris BB, Desnoyer R, Klepin HD, Hosseinzadeh K, Clark C, Cameron A, Leyendecker J, D'Agostino R Jr, Topaloglu U, et al: Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: A single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol. 18:770–778. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Philip PA, Buyse ME, Alistar AT, Rocha Lima CM, Luther S, Pardee TS and Van Cutsem E: A phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. Future Oncol. 15:3189–3196. 2019. View Article : Google Scholar : PubMed/NCBI |