Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Open accessAbstract
Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent. Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible Kras(G12D)-driven PDAC mouse model establishes that advanced PDAC remains strictly dependent on Kras(G12D) expression. Transcriptome and metabolomic analyses indicate that Kras(G12D) serves a vital role in controlling tumor metabolism through stimulation of glucose uptake and channeling of glucose intermediates into the hexosamine biosynthesis and pentose phosphate pathways (PPP). These studies also reveal that oncogenic Kras promotes ribose biogenesis. Unlike canonical models, we demonstrate that Kras(G12D) drives glycolysis intermediates into the nonoxidative PPP, thereby decoupling ribose biogenesis from NADP/NADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in PDAC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic ablation of KRAS expression leads to cell cycle arrest and death in cell lines and potent tumor regressions in animal models of PDAC.
“Prior studies have demonstrated that genetic ablation of KRAS expression leads to cell cycle arrest and death in cell lines and potent tumor regressions in animal models of PDAC (5–7).”
From Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer (2024) · cites this paper as [6]
In “Kras G12D Is Essential for PDAC Maintenance” (p. 4), Kras extinction caused rapid regression of mouse PDAC tumors, with reduced proliferation and increased apoptosis. The same section reports loss of clonogenic growth in cultured primary tumor cells, but does not establish cell-cycle arrest and death in those cells. (LLM, conf=0.85)
Experimental — accuracy not yet measuredGlycolysis is a critical downstream effector of oncogenic KRAS signaling in advanced tumors.
“Consistent with our previous findings on the role of glycolysis as a critical downstream effector of oncogenic KRAS signaling in advanced tumors,16,17”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [17]
The Discussion (p. 8) says oncogenic Kras controls glycolysis in fully established pancreatic ductal adenocarcinoma (PDAC), and the Results (p. 5) show reduced glycolytic flux after Kras inactivation. The evidence is specific to PDAC; it does not establish glycolysis as a critical downstream effector across advanced tumors generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn the iKras GEM model, acute extinction of mutant KRAS results in downregulation of SDC1 expression, coinciding with suppression of MAPK signaling.
“In the iKras GEM model, acute extinction of mutant KRAS results in downregulation of SDC1 expression, coinciding with suppression of MAPK signaling, as evidenced by reduced ERK phosphorylation.12,17”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [17]
In “Kras G12D Is Essential for PDAC Maintenance” (p. 5), the paper reports decreased MAPK signaling, measured by phospho-Erk, as early as 24 hours after doxycycline withdrawal in the iKras model. Our copy does not report downregulation of SDC1 expression; searches for SDC1 and syndecan did not find support for that part of the claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredKRAS mutations lead to sustained activation of MAPK and PI3K-mTOR pathways.
“KRAS mutations lead to sustained activation of MAPK and PI3K-mTOR pathways16,17”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [16]
Pancreatic ductal adenocarcinoma (PDAC) lines were chosen because cancers of the pancreas are characterized by rapid progression, invasiveness, and elevated fermentative metabolism.
“Pancreatic ductal adenocarcinoma (PDAC) lines were chosen for our study because cancers of the pancreas are characterized by rapid progression,9,10 invasiveness,11,12 and elevated fermentative metabolism.13,14,15,16”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [16]
Pancreatic cancers generate substantial lactic acid fluxes, linked to mutations that promote hyper-proliferation.
“pancreatic cancers generate substantial lactic acid fluxes, linked to mutations that promote hyper-proliferation”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [16]
KRAS promotes the non-oxidative arm of the pentose phosphate pathway, supplying ribose for nucleic acid production.
“KRAS also promotes the hexosamine biosynthesis pathway (HBP), which provides precursors for lipid and protein glycosylation34, and the non-oxidative arm of the pentose phosphate pathway (PPP)28, which supplies ribose, the backbone for nucleic acid production35 (Fig 2).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [28]
KRAS regulates these metabolic pathways through MAPK-dependent signaling, supporting survival and conferring a proliferative advantage on tumors.
“KRAS regulates these pathways through MAPK-dependent signaling cascades, ultimately supporting cell survival and conferring a proliferative advantage on tumors28,36,37.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [28]
Oncogenic KRAS upregulates PFK1, ENO1, and LDHA, promoting glycolytic flux and production of intermediates that can enter anabolic pathways.
“Oncogenic KRAS also upregulates expression of other key glycolytic enzymes, such as PFK1, ENO1, and LDHA28,31–33, thereby promoting glycolytic flux and enabling the production of glycolytic intermediates that can be shunted into other anabolic pathways (Fig 2).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [28]
Mutant KRAS upregulates GLUT1 to increase glucose uptake and induces HK1 and HK2 to increase glycolytic activity.
“Gene expression and metabolic flux analyses have shown that it upregulates the expression of the GLUT1 glucose transporter to promote glucose uptake by cells, as well as inducing expression of hexokinase 1 and 2 (HK1 and HK2) rate-limiting enzymes of glycolysis, to increase glycolytic activity27–30 (Fig. 2a).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [28]
Mouse PDAC tumors driven by mutant Kras experience metabolic alteration and are dependent on glucose and glutamine.
“Mouse PDAC tumors driven by mutant Kras also experience metabolic alteration and are dependent on glucose and glutamine (73, 77).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [73]
Extinguishing mutant Kras expression in the pancreas led to rapid tumor regression, demonstrating a critical role of Kras in tumor maintenance.
“Extinguishing the expression of mutant Kras in the pancreas led to rapid tumor regression, thus demonstrating a critical role of Kras in tumor maintenance (73, 78).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [73]
In inducible GEMMs, withdrawal of oncogenic Kras resulted in regression of invasive neoplasia, including metastatic disease.
“Withdrawal of oncogenic Kras resulted in regression of invasive neoplasia, including regression of metastatic disease63–65.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [64]
The non-oxidative pentose phosphate pathway enables nucleotide biosynthesis, and the hexosamine biosynthesis pathway generates GlcNAc for posttranslational modifications.
“Examples include the non-oxidative pentose phosphate pathway, which enables nucleotide biosynthesis, and the hexosamine biosynthesis pathway, which generates GlcNAc required for posttranslational modifications64,195”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [64]
Mutant KRAS drives upregulated glycolysis, increasing lactate production and providing carbon inputs for synthesis of molecules required for proliferation.
“Mutant KRAS drives upregulated glycolysis, not only increasing production of lactate, but also providing key carbon inputs for synthesis of molecules required for proliferation.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [64]
NRF2-mediated metabolic reprogramming and regulation of redox homeostasis likely underpin the strong co-selection of KEAP1 with LKB1 and KRAS mutations in NSCLC.
“Thus, NRF2- mediated metabolic reprogramming and regulation of redox homeostasis likely underpin the strong co-selection of KEAP1 with LKB1 and KRAS mutations in NSCLC at least partially because oncogenic KRAS itself promotes oxidative stress and anabolic metabolism and because KL NSCLC cells depend on the pentose phosphate pathway for NAPDH generation and for detoxification of reactive oxygen”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [98]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Self-citationSmyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202 · see citing works
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088 · see citing works
Hidalgo, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0901557 · Cited by 2,570 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277 · see citing works
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · see citing works
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001 · see citing works
Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683 · see citing works
Genetics and biology of pancreatic ductal adenocarcinomaPreprint
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. M., & DePinho, R. A. (2006) · Genes & Development · doi:10.1101/gad.1415606 · Cited by 1,570 · see citing works
Self-citationThe sweet and sour of cancer: glycans as novel therapeutic targets
Fuster, M. M., & Esko, J. D. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1649 · Cited by 1,389 · see citing works
The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
Levine, A. J., & Puzio-Kuter, A. M. (2010) · Science · doi:10.1126/science.1193494 · Cited by 1,243 · see citing works
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179 · see citing works
Yuan, M., Breitkopf, S. B., Yang, X., & Asara, J. M. (2012) · Nature Protocols · doi:10.1038/nprot.2012.024 · Cited by 1,122 · see citing works
Self-citationPhosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120 · see citing works
Self-citationAguirre, A. J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D. A., Horner, J., Redston, M. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1158703 · Cited by 1,033 · cited 2× · see citing works
“Genetically engineered mouse models (GEMM) have provided evidence for oncogenic Kras (KrasG12D) as a major driver in PDAC initiation, with the aforementioned tumor suppressor genes constraining progression (Aguirre et al., 2003; Guerra et al., 2003; Hingorani et al., 2003).”
Self-citationBrick by brick: metabolism and tumor cell growth
DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018 · see citing works
The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R. J., & Wright, C. V. E. (2002) · Nature Genetics · doi:10.1038/ng959 · Cited by 1,007 · cited 2× · see citing works
“These mice were crossed to ROSA26-LSL-rtTA-IRES-GFP (ROSA_rtTA) (Belteki et al., 2005) and p48-Cre (Kawaguchi et al., 2002) mice to enable pancreas-specific and doxycycline (doxy)-inducible expression of KrasG12D (Figure S1B).”
Essential role for oncogenic Ras in tumour maintenance
Chin, L., Tam, A., Pomerantz, J. H., Wong, M., Holash, J., Bardeesy, N., Shen, Q., O'Hagan, R., Pantginis, J., Zhou, H., et al. (1999) · Nature · doi:10.1038/22788 · Cited by 928 · see citing works
Self-citationMarino, S., Vooijs, M., van der Gulden, H., Jonkers, J., & Berns, A. (2000) · Genes & Development · doi:10.1101/gad.14.8.994 · Cited by 920 · see citing works
Reversible tumorigenesis by MYC in hematopoietic lineages.
Felsher, D., & Bishop, J. (1999) · Molecules and Cells · doi:10.1016/s1097-2765(00)80367-6 · Cited by 917 · see citing works
Glucose Deprivation Contributes to the Development of <i>KRAS</i> Pathway Mutations in Tumor Cells
Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Willson, J. K. V., Markowitz, S., Zhou, S., et al. (2009) · Science · doi:10.1126/science.1174229 · Cited by 914 · see citing works
Singh, A., Greninger, P., Rhodes, D., Koopman, L., Violette, S., Bardeesy, N., & Settleman, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.022 · Cited by 841 · see citing works
Modelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 822 · see citing works
p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase
Jiang, P., Du, W., Wang, X., Mancuso, A., Gao, X., Wu, M., & Yang, X. (2011) · Nature Cell Biology · doi:10.1038/ncb2172 · Cited by 798 · see citing works
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
Zheng, H., Ying, H., Yan, H., Kimmelman, A. C., Hiller, D. J., Chen, A.-J., Perry, S. R., Tonon, G., Chu, G. C., Ding, Z., et al. (2008) · Nature · doi:10.1038/nature07443 · Cited by 767 · see citing works
Self-citationStromal biology and therapy in pancreatic cancer
Neeße, A., Michl, P., Frese, K. K., Feig, C., Cook, N., Jacobetz, M. A., Lolkema, M. P., Buchholz, M., Olive, K. P., Gress, T. M., et al. (2010) · Gut · doi:10.1136/gut.2010.226092 · Cited by 758 · see citing works
Rinehart, J., Adjei, A. A., LoRusso, P. M., Waterhouse, D., Hecht, J. R., Natale, R. B., Hamid, O., Varterasian, M., Asbury, P., Kaldjian, E. P., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.01.185 · Cited by 645 · see citing works
Hart, G. W., & Copeland, R. J. (2010) · Cell · doi:10.1016/j.cell.2010.11.008 · Cited by 643 · see citing works
Fisher, G. H., Wellen, S. L., Klimstra, D., Lenczowski, J. M., Tichelaar, J. W., Lizak, M. J., Whitsett, J. A., Koretsky, A., & Varmus, H. E. (2001) · Genes & Development · doi:10.1101/gad.947701 · Cited by 582 · see citing works
Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
Guerra, C. E., Mijimolle, N., Dhawahir, A., Dubus, P. R., Barradas, M., Serrano, M., Campuzano, V., & Barbacid, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00191-0 · Cited by 566 · see citing works
Belteki, G., Haigh, J., Kabacs, N., Haigh, K., Sison, K., Costantini, F., Whitsett, J., Quaggin, S., & Nagy, A. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni051 · Cited by 423 · see citing works
Wellen, K. E., Lu, C., Mancuso, A., Lemons, J. M. S., Ryczko, M., Dennis, J. W., Rabinowitz, J. D., Coller, H. A., & Thompson, C. B. (2010) · Genes & Development · doi:10.1101/gad.1985910 · Cited by 377 · see citing works
The molecular determinants of de novo nucleotide biosynthesis in cancer cells
Tong, X., Zhao, F., & Thompson, C. B. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.01.002 · Cited by 351 · see citing works
Moody, S. E., Sarkisian, C. J., Hahn, K. T., Gunther, E. J., Pickup, S., Dugan, K. D., Innocent, N., Cardiff, R. D., Schnall, M. D., & Chodosh, L. A. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00212-x · Cited by 345 · see citing works
Therapeutic Strategies for Targeting Ras Proteins
Gysin, S., Salt, M. B., Young, A. E., & McCormick, F. (2011) · Genes & Cancer · doi:10.1177/1947601911412376 · Cited by 321 · see citing works
Funes, J. M., Quintero, M., Henderson, S. R., Martínez, D., Qureshi, U., Westwood, C., Clements, M. O., Bourboulia, D., Pedley, R. B., Moncada, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700690104 · Cited by 256 · see citing works
Glycolysis and methylaminoisobutyrate uptake in rat-1 cells transfected with ras or myc oncogenes.
Racker, E., Resnick, R. J., & Feldman, R. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.11.3535 · Cited by 135 · see citing works
Clasquin, M. F., Melamud, E., Singer, A. U., Gooding, J. R., Xu, X., Dong, A., Cui, H., Campagna, S. R., Savchenko, A. V., Yakunin, A. F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.05.022 · Cited by 121 · see citing works
Fujita, H., Ohuchida, K., Mizumoto, K., Nakata, K., Yu, J., Kayashima, T., Cui, L., Manabe, T., Ohtsuka, T., & Tanaka, M. (2010) · Pancreas · doi:10.1097/mpa.0b013e3181dbf647 · Cited by 118 · see citing works
K-ras Codon-Specific Mutations Produce Distinctive Metabolic Phenotypes in Human Fibroblasts
Vizán, P., Boros, L. G., Figueras, A., Capellá, G., Mangues, R., Bassilian, S., Lim, S. K., Lee, W. P., & Cascante, M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0074 · Cited by 115 · see citing works
Boros, L. G., Lee, P. W. N., Brandes, J. L., Cascante, M., Muscarella, P., Schirmer, W. J., Melvin, W. S., & Ellison, E. C. (1998) · Medical Hypotheses · doi:10.1016/s0306-9877(98)90178-5 · Cited by 111 · see citing works
Jw, D., Kosh, K., Bryce, D. M., & Ml, B. (1989) · PubMed · Cited by 94 · see citing works
Bolscher, J. G. M., van der Bijl, M. M., Neefjes, J., Hall, A., Smets, L. A., & Ploegh, H. L. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03208.x · Cited by 61 · see citing works
The pentose pathway: A random harvest
Williams, J. F., Arora, K. K., & Longenecker, J. P. (1987) · International Journal of Biochemistry · doi:10.1016/0020-711x(87)90239-4 · Cited by 52 · see citing works
Altered Detoxification Status and Increased Resistance to Oxidative Stress by K-Ras Transformation
Recktenwald, C. V., Kellner, R., Lichtenfels, R., & Seliger, B. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0360 · Cited by 51 · see citing works
Boros, L., Lerner, M. R., Morgan, D. L., Taylor, S. L., Smith, B. J., Postier, R. G., & Brackett, D. J. (2005) · Pancreas · doi:10.1097/01.mpa.0000186524.53253.fb · Cited by 48 · see citing works
Proteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Metabolic Alterations
Zhou, W., Capello, M., Fredolini, C., Piemonti, L., Liotta, L. A., Novelli, F., & Petricoin, E. F. (2011) · Journal of Proteome Research · doi:10.1021/pr101179t · Cited by 45 · see citing works
Oncogenic K-ras “addiction” and synthetic lethality
Singh, A., & Settleman, J. (2009) · Cell Cycle · doi:10.4161/cc.8.17.9336 · Cited by 44 · see citing works
Wojciechowicz, D. C., Park, P. Y., & Paty, P. B. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2034 · Cited by 23 · see citing works
Rak, J. W., Basolo, F., Elliott, J. W., Russo, J., & Miller, F. R. (1991) · Cancer Letters · doi:10.1016/0304-3835(91)90059-q · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170 · see citing works
The Warburg Effect: How Does it Benefit Cancer Cells?
Liberti, M. V., & Locasale, J. W. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.001 · Cited by 5,150 · see citing works
Self-citationThe biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366 · see citing works
Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740 · see citing works
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., Lee, J. J., & Kalluri, R. (2017) · Nature · doi:10.1038/nature22341 · Cited by 2,639 · see citing works
Ryan, D. P., Hong, T. S., & Bardeesy, N. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1404198 · Cited by 2,348 · see citing works
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,316 · see citing works
Organoid models of human and mouse ductal pancreatic cancer
Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150 · see citing works
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990 · see citing works
Self-citationZheng, X., Carstens, J. L., Kim, J., Scheible, M., Kaye, J. A., Sugimoto, H., Wu, C.-C., LeBleu, V. S., & Kalluri, R. (2015) · Nature · doi:10.1038/nature16064 · Cited by 2,018 · see citing works
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
Self-citationKleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638 · see citing works
Reprogramming of fatty acid metabolism in cancer
Koundouros, N., & Poulogiannis, G. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0650-z · Cited by 1,621 · see citing works
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho, P.-C., Bihuniak, J. D., Macintyre, A. N., Staron, M., Liu, X., Amezquita, R., Tsui, Y.-C., Cui, G., Micevic, G., Perales, J. C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.012 · Cited by 1,462 · see citing works
Self-citationMetabolic pathways promoting cancer cell survival and growth
Boroughs, L. K., & DeBerardinis, R. J. (2015) · Nature Cell Biology · doi:10.1038/ncb3124 · Cited by 1,459 · see citing works
The pentose phosphate pathway and cancer
Patra, K. C., & Hay, N. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.06.005 · Cited by 1,444 · see citing works
Lipid metabolic reprogramming in cancer cells
Beloribi‐Djefaflia, S., Vasseur, S., & Guillaumond, F. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.49 · Cited by 1,392 · see citing works
Lactate Metabolism in Human Lung Tumors
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343 · see citing works
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works
Self-citationTumor-selective catalytic nanomedicine by nanocatalyst delivery
Huo, M., Wang, L., Chen, Y., & Shi, J. (2017) · Nature Communications · doi:10.1038/s41467-017-00424-8 · Cited by 1,327 · see citing works
ERK signalling: A master regulator of cell behaviour, life and fate
Lavoie, H., Gagnon, J., & Therrien, M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0255-7 · Cited by 1,185 · see citing works
Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
Viale, A., Pettazzoni, P., Lyssiotis, C. A., Ying, H., Sánchez, N., Marchesini, M., Carugo, A., Green, T., Seth, S., Giuliani, V., et al. (2014) · Nature · doi:10.1038/nature13611 · Cited by 1,259 · see citing works
Self-citationAutophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
Self-citationPancreatic stellate cells support tumour metabolism through autophagic alanine secretion
Sousa, C. M., Biancur, D. E., Wang, X., Halbrook, C. J., Sherman, M. H., Zhang, L., Kremer, D., Hwang, R. F., Witkiewicz, A. K., Ying, H., et al. (2016) · Nature · doi:10.1038/nature19084 · Cited by 1,122 · see citing works
Self-citationCo-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.126 · Cited by 1,038 · see citing works
Signal Transduction in CancerPreprint
Sever, R., & Brugge, J. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006098 · Cited by 992 · see citing works
Regulation of mammalian nucleotide metabolism and biosynthesis
Lane, A. N., & Fan, T. W.-M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv047 · Cited by 959 · see citing works
Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927 · see citing works
Cancer Cell Metabolism: One Hallmark, Many Faces
Cantor, J. R., & Sabatini, D. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0345 · Cited by 945 · see citing works
How cancer metabolism is tuned for proliferation and vulnerable to disruption
Schulze, A., & Harris, A. L. (2012) · Nature · doi:10.1038/nature11706 · Cited by 927 · see citing works
Yun, J., Mullarky, E., Lu, C., Bosch, K. N., Kavalier, A., Rivera, K., Roper, J., Chio, I. I. C., Giannopoulou, E. G., Rago, C., et al. (2015) · Science · doi:10.1126/science.aaa5004 · Cited by 913 · see citing works
Self-citationKamphorst, J. J., Nofal, M., Commisso, C., Hackett, S. R., Lu, W., Grabocka, E., Vander Heiden, M. G., Miller, G., Drebin, J. A., Bar-Sagi, D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2211 · Cited by 893 · see citing works
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853 · see citing works
Self-citationKRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Waters, A. M., & Der, C. J. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031435 · Cited by 875 · see citing works
Glutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · see citing works
Patra, K. C., Wang, Q., Bhaskar, P. T., Miller, L. L., Wang, Z., Wheaton, W. W., Chandel, N. S., Laakso, M., Muller, W. J., Allen, E. L., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.014 · Cited by 856 · see citing works
Stephen, A. G., Esposito, D., Bagni, R. K., & McCormick, F. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.017 · Cited by 795 · see citing works
Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer
Davidson, S. M., Papagiannakopoulos, T., Olenchock, B. A., Heyman, J. E., Keibler, M. A., Luengo, A., Bauer, M. R., Jha, A. K., O’Brien, J. P., Pierce, K. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.007 · Cited by 737 · see citing works
Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1
Ben-Sahra, I., Howell, J. J., Asara, J. M., & Manning, B. D. (2013) · Science · doi:10.1126/science.1228792 · Cited by 739 · see citing works
Self-citationYap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer
Kapoor, A., Yao, W., Ying, H., Hua, S., Liewen, A., Wang, Q., Zhong, Y., Wu, C.-J., Sadanandam, A., Hu, B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.003 · Cited by 716 · see citing works
Self-citationTumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 772 · see citing works
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Bryant, K. L., Stalnecker, C. A., Zeitouni, D., Klomp, J. E., Peng, S., Tikunov, A. P., Gunda, V., Pierobon, M., Waters, A. M., George, S. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0368-8 · Cited by 692 · see citing works
Self-citationKamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307237110 · Cited by 726 · see citing works
Metabolic targets for cancer therapy
Galluzzi, L., Kepp, O., Heiden, M. G. V., & Kroemer, G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4145 · Cited by 705 · see citing works
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.008 · Cited by 706 · see citing works
KRAS: feeding pancreatic cancer proliferation
Bryant, K. L., Mancias, J. D., Kimmelman, A. C., & Der, C. J. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.12.004 · Cited by 675 · see citing works
Self-citationMetabolomics in cancer research and emerging applications in clinical oncology
Schmidt, D. R., Patel, R., Kirsch, D. G., Lewis, C. A., Heiden, M. G. V., & Locasale, J. W. (2021) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21670 · Cited by 652 · see citing works
Self-citationCellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets
Di, X., Gao, X., Peng, L., Ai, J., Jin, X., Qi, S., Li, H., Wang, K., & Luo, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01501-9 · Cited by 660 · see citing works
Modulating the therapeutic response of tumours to dietary serine and glycine starvation
Maddocks, O. D. K., Athineos, D., Cheung, E. C., Lee, P., Zhang, T., van den Broek, N. J. F., Mackay, G. M., Labuschagne, C. F., Gay, D., Kruiswijk, F., et al. (2017) · Nature · doi:10.1038/nature22056 · Cited by 603 · see citing works
A roadmap for interpreting 13C metabolite labeling patterns from cells
Buescher, J. M., Antoniewicz, M. R., Boros, L. G., Burgess, S. C., Brunengraber, H., Clish, C. B., DeBerardinis, R. J., Féron, O., Frezza, C., Ghesquière, B., et al. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.02.003 · Cited by 623 · see citing works
Self-citationPathways of Colorectal Carcinogenesis
Nguyen, L. H., Goel, A., & Chung, D. C. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.08.059 · Cited by 606 · see citing works
Sullivan, M. R., Danai, L. V., Lewis, C. A., Chan, S. H., Gui, D. Y., Kunchok, T., Dennstedt, E. A., Vander Heiden, M. G., & Muir, A. (2019) · eLife · doi:10.7554/elife.44235 · Cited by 588 · see citing works
Tang, T., Huang, X., Zhang, G., Hong, Z., Bai, X., & Liang, T. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00449-4 · Cited by 613 · see citing works
Abdel-Wahab, A. F., Mahmoud, W., & Al-Harizy, R. M. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104511 · Cited by 589 · see citing works
Fiaschi, T., Marini, A., Giannoni, E., Taddei, M. L., Gandellini, P., Donatis, A. D., Lanciotti, M., Serni, S., Cirri, P., & Chiarugi, P. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1949 · Cited by 586 · see citing works
Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation
Lee, J. V., Carrer, A., Shah, S., Snyder, N. W., Wei, S., Venneti, S., Worth, A. J., Yuan, Z.-F., Lim, H.-W., Liu, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.06.004 · Cited by 563 · see citing works
RAF-MEK-ERK pathway in cancer evolution and treatment
Ullah, R., Yin, Q., Snell, A. H., & Wan, L. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.010 · Cited by 553 · see citing works
Stromal biology and therapy in pancreatic cancer: a changing paradigm
Neeße, A., Algül, H., Tuveson, D. A., & Gress, T. M. (2015) · Gut · doi:10.1136/gutjnl-2015-309304 · Cited by 562 · see citing works
Regulation of the pentose phosphate pathway in cancer
Jiang, P., Du, W., & Wu, M. (2014) · Protein & Cell · doi:10.1007/s13238-014-0082-8 · Cited by 568 · see citing works
Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression
Wang, G., Lü, X., Dey, P., Deng, P., Wu, C.-C., Jiang, S., Fang, Z., Zhao, K., Konaparthi, R., Hua, S., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0224 · Cited by 556 · see citing works
Self-citationCancer Metabolism: Phenotype, Signaling and Therapeutic Targets
Park, J. H., Pyun, W. Y., & Park, H. W. (2020) · Cells · doi:10.3390/cells9102308 · Cited by 558 · see citing works
Shukla, S. K., Purohit, V., Mehla, K., Gunda, V., Chaika, N. V., Vernucci, E., King, R. J., Abrego, J., Goode, G. D., Dasgupta, A., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.06.004 · Cited by 542 · see citing works
Self-citationG-quadruplexes: a promising target for cancer therapy
Kosiol, N., Juranek, S., Brossart, P., Heine, A., & Paeschke, K. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01328-4 · Cited by 540 · see citing works
Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells
Eling, N., Reuter, L., Hazin, J., Hamacher-Brady, A., & Brady, N. R. (2015) · Oncoscience · doi:10.18632/oncoscience.160 · Cited by 524 · see citing works
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527 · see citing works
Self-citationOncogenic KRAS signalling in pancreatic cancer
Eser, S., Schnieke, A., Schneider, G., & Saur, D. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.215 · Cited by 504 · see citing works
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 502 · see citing works
Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations
Yang, A., Rajeshkumar, N. V., Wang, X., Yabuuchi, S., Alexander, B. M., Chu, G. C., Von Hoff, D. D., Maitra, A., & Kimmelman, A. C. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0362 · Cited by 486 · see citing works
Self-citationMultidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma
Grossberg, A. J., Chu, L. C. H., Deig, C. R., Fishman, E. K., Hwang, W. L., Maitra, A., Marks, D. L., Mehta, A., Nabavizadeh, N., Simeone, D. M., et al. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21626 · Cited by 491 · see citing works
Guillaumond, F., Bidaut, G., Ouaissi, M., Servais, S., Gouirand, V., Olivares, O., Lac, S., Borge, L., Roques, J., Gayet, O., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421601112 · Cited by 454 · see citing works
Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance
Sherman, M. H., & Beatty, G. L. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031621-024600 · Cited by 481 · see citing works
Zhang, L., Wang, Z., Zhang, Y., Cao, F., Dong, K., Ren, J., & Qu, X. (2018) · ACS Nano · doi:10.1021/acsnano.8b05200 · Cited by 446 · see citing works
Ferrer, C. M., Lynch, T. P., Sodi, V. L., Falcone, J. N., Schwab, L. P., Peacock, D. L., Vocadlo, D. J., Seagroves, T. N., & Reginato, M. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.04.026 · Cited by 446 · see citing works
Hofmann, M. H., Gmachl, M., Ramharter, J., Savarese, F., Gerlach, D., Marszalek, J. R., Sanderson, M. P., Kessler, D., Trapani, F., Arnhof, H., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0142 · Cited by 444 · see citing works
Guillaumond, F., Leca, J., Olivares, O., Lavaut, M.-N., Vidal, N., Berthezène, P., Dusetti, N. J., Loncle, C., Calvo, E., Turrini, O., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219555110 · Cited by 413 · see citing works
Daemen, A., Peterson, D., Sahu, N., McCord, R., Du, X., Liu, B., Kowanetz, K., Hong, R., Moffat, J., Gao, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501605112 · Cited by 398 · see citing works
Altered metabolite levels in cancer: implications for tumour biology and cancer therapy
Sullivan, L. B., Gui, D. Y., & Heiden, M. G. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.85 · Cited by 406 · see citing works
Olivares, O., Mayers, J. R., Gouirand, V., Torrence, M. E., Gicquel, T., Borge, L., Lac, S., Roques, J., Lavaut, M.-N., Berthezène, P., et al. (2017) · Nature Communications · doi:10.1038/ncomms16031 · Cited by 413 · see citing works
Therapeutic strategies to target RAS-mutant cancers
Ryan, M. B., & Corcoran, R. B. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0105-0 · Cited by 420 · see citing works
Targeting hypoxic tumor microenvironment in pancreatic cancer
Tao, J., Yang, G., Zhou, W., Qiu, J., Chen, G., Luo, W., Zhao, F., You, L., Zheng, L., Zhang, T., et al. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01030-w · Cited by 419 · see citing works
Metabolism of pancreatic cancer: paving the way to better anticancer strategies
Qin, C., Yang, G., Yang, J., Ren, B., Wang, H., Chen, G., Zhao, F., You, L., Wang, W., & Zhao, Y. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01169-7 · Cited by 415 · see citing works
Self-citationThe Role of the Pentose Phosphate Pathway in Diabetes and Cancer
Ge, T., Yang, J., Zhou, S., Wang, Y., Li, Y., & Tong, X. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00365 · Cited by 413 · see citing works
Self-citationHu, K., Li, K., Lv, J., Feng, J., Chen, J., Wu, H., Cheng, F., Jiang, W., Wang, J., Pei, H., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124049 · Cited by 409 · see citing works
Papke, B., & Der, C. J. (2017) · Science · doi:10.1126/science.aam7622 · Cited by 399 · see citing works
Roles for KRAS in Pancreatic Tumor Development and Progression
di Magliano, M. P., & Logsdon, C. D. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.071 · Cited by 397 · see citing works
Mitochondria as biosynthetic factories for cancer proliferation
Ahn, C. S., & Metallo, C. M. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0128-2 · Cited by 399 · see citing works
Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis
Thomas, D., & Radhakrishnan, P. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0927-5 · Cited by 399 · see citing works
Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer
Halbrook, C. J., & Lyssiotis, C. A. (2017) · Cancer Cell · doi:10.1016/j.ccell.2016.12.006 · Cited by 394 · see citing works
Self-citationThe Keap1–Nrf2 system in cancers: stress response and anabolic metabolism
Mitsuishi, Y., Motohashi, H., & Yamamoto, M. P. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00200 · Cited by 394 · see citing works
Serasinghe, M. N., Wieder, S. Y., Renault, T. T., Elkholi, R., Asciolla, J. J., Yao, J. L., Jabado, O., Hoehn, K. L., Kageyama, Y., Sesaki, H., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.003 · Cited by 388 · see citing works
NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
Chio, I. I. C., Jafarnejad, S. M., Ponz-Sarvise, M., Park, Y., Rivera, K., Palm, W., Wilson, J., Sangar, V., Hao, Y., Öhlund, D., et al. (2016) · Cell · doi:10.1016/j.cell.2016.06.056 · Cited by 378 · see citing works
“Hif1a likely contributes to the glycolytic phenotype of PDA (Ying et al., 2012), working in parallel with NRF2 transcriptional target genes that are metabolic enzymes governing the pentose phosphate pathway (Mitsuishi et al., 2012) to promote metabolic rewiring in cancer cells.”
Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review
Kontomanolis, E. N., Koutras, A., Syllaios, A., Schizas, D., Mastoraki, A. T., Garmpis, N., Diakosavvas, M., Angelou, K., Tsatsaris, G., Pagkalos, A., et al. (2020) · Anticancer Research · doi:10.21873/anticanres.14622 · Cited by 389 · see citing works
Nutrient acquisition strategies of mammalian cells
Palm, W., & Thompson, C. B. (2017) · Nature · doi:10.1038/nature22379 · Cited by 388 · see citing works
Efficacy of a small-molecule inhibitor of KrasG12D in immunocompetent models of pancreatic cancer
Kemp, S. B., Cheng, N., Markosyan, N., Sor, R., Kim, I.-K., Hallin, J., Shoush, J., Quinones, L., Brown, N. V., Bassett, J. B., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1066 · Cited by 370 · see citing works
The ERK and JNK pathways in the regulation of metabolic reprogramming
Papa, S., Choy, P. M., & Bubici, C. (2018) · Oncogene · doi:10.1038/s41388-018-0582-8 · Cited by 381 · see citing works
Four Key Steps Control Glycolytic Flux in Mammalian Cells
Tanner, L. B., Goglia, A. G., Wei, M. H., Sehgal, T., Parsons, L. R., Park, J. O., White, E., Toettcher, J. E., & Rabinowitz, J. D. (2018) · Cell Systems · doi:10.1016/j.cels.2018.06.003 · Cited by 368 · see citing works
- Authors
- Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., Yan, H., Wang, W., Chen, S., Viale, A., Zheng, H., Paik, J.-H., Lim, C., Guimaraes, A. R., Martin, E. S., Chang, J., Hezel, A. F., Perry, S. R., Hu, J., Gan, B., Xiao, Y., Asara, J. M., Weissleder, R., Wang, Y. A., Chin, L., Cantley, L. C., & DePinho, R. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kimmelman, Alec C.
- DePinho, Ronald A.
- ORCID
- Ying, Haoqiang
- Kimmelman, Alec C.
- Lyssiotis, Costas A.
- Locasale, Jason W.
- Son, Jaekyoung
- Zhang, Hailei
- Coloff, Jonathan L.
- Yan, Haiyan
- Wang, Wei
- Chen, Shujuan
- Viale, Andrea
- Zheng, Hongwu
- Martin, Eric S.
- Hezel, Aram F.
- Hu, Jian
- Gan, Boyi
- Xiao, Yonghong
- Asara, John M.
- Weissleder, Ralph
- Wang, Y. Alan
- Cantley, Lewis C.
- DePinho, Ronald A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 149
- Issue
- 3
- Pages
- 656-670
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3472002
- OpenAlex
- W2069269337
- Cited by
- 2,043
- References
- 55
- Citations by year
- 2026: 139 · 2025: 129 · 2024: 154 · 2023: 175 · 2022: 178 · 2021: 200 · 2020: 153 · 2019: 164 · 2018: 135 · 2017: 153 · 2016: 139 · 2015: 114 · 2014: 105 · 2013: 79 · 2012: 23
- FWCI
- 50.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Cancer Institute (P50-CA-86355, U24CA092782, P50CA086355, T32CA009382, R01CA157490, P01CA120964, P01CA117969, P30CA006516)
- National Institute of General Medical Sciences (R01GM056203)
- National Institute of Biomedical Imaging and Bioengineering (K08EB012859)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- oncogenic KRAS, pancreatic ductal adenocarcinoma, tumor maintenance, glucose metabolism, metabolic reprogramming, hexosamine biosynthetic pathway, pentose phosphate pathway, glycolysis intermediates, cancer metabolism
- MeSH terms
- Adenocarcinoma, Animals, Disease Models, Animal, Humans, Pancreatic Neoplasms, Transcription, Genetic, Proto-Oncogene Proteins p21(ras), Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
