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Review

Critical role of oncogenic KRAS in pancreatic cancer (Review)

  • Authors:
    • Jiang Liu
    • Shunrong Ji
    • Chen Liang
    • Yi Qin
    • Kaizhou Jin
    • Dingkon Liang
    • Wenyan Xu
    • Si Shi
    • Bo Zhang
    • Liang Liu
    • Chen Liu
    • Jin Xu
    • Quanxing Ni
    • Xianjun Yu
  • View Affiliations / Copyright

    Affiliations: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
  • Pages: 4943-4949
    |
    Published online on: April 27, 2016
       https://doi.org/10.3892/mmr.2016.5196
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Abstract

Pancreatic cancer is a human malignancy with one of the highest mortality rates and little progress has been achieved in its treatment in recent decades. Further improvement to the understanding of the biological and molecular mechanisms underlying the initiation and development of pancreatic ductal adenocarcinoma (PDAC) is required. Previous studies using genetically engineered mouse models have demonstrated that oncogenic GTPase KRas (KRAS) mutation is involved in the formation of pancreatic intraepithelial neoplasia and promotes the progression of PDAC. However, attempts to target KRAS directly by pharmacological inhibition have been unsuccessful. This has resulted in increased efforts to identify pharmacological targets and nodes associated with the mutated KRAS. The present review discusses the recent progress and prospects of KRAS signaling in pancreatic cancer.
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1 

National Cancer Institute: SEER stat fact sheets, pancreas. http://seer.cancer.gov/statfacts/html/pancreas.html. Accessed April 15, 2016.

2 

Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr and Kinzler KW: Cancer genome landscapes. Science. 339:1546–1558. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Wood LD and Hruban RH: Pathology and molecular genetics of pancreatic neoplasms. Cancer J. 18:492–501. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N and Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 53:549–554. 1988. View Article : Google Scholar : PubMed/NCBI

5 

Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ and Bos JL: KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 16:7773–7782. 1988. View Article : Google Scholar : PubMed/NCBI

6 

Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ and Wright CV: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet. 32:128–134. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, Ross S, Conrads TP, Veenstra TD, Hitt BA, et al: Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 4:437–450. 2003. View Article : Google Scholar

8 

Olive KP and Tuveson DA: The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin Cancer Res. 12:5277–5287. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Morris JP IV, Wang SC and Hebrok M: KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 10:683–695. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, Redston MS and DePinho RA: Activated KRAS and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 17:3112–3126. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S and Tuveson DA: Trp53R172H and KRASG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 7:469–483. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Singh M, Lima A, Molina R, Hamilton P, Clermont AC, Devasthali V, Thompson JD, Cheng JH, Bou Reslan H, Ho CC, et al: Assessing therapeutic responses in KRAS mutant cancers using genetically engineered mouse models. Nat Biotechnol. 28:585–593. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Carrière C, Young AL, Gunn JR, Longnecker DS and Korc M: Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic KRAS in the nestin cell lineage. PLoS One. 6:e277252011. View Article : Google Scholar : PubMed/NCBI

14 

Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA and Vonderheide RH: Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 67:9518–9527. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Won JH, Zhang Y, Ji B, Logsdon CD and Yule DI: Phenotypic changes in mouse pancreatic stellate cell Ca2+ signaling events following activation in culture and in a disease model of pancreatitis. Mol Biol Cell. 22:421–436. 2011. View Article : Google Scholar :

16 

Erkan M, Adler G, Apte MV, Bachem MG, Buchholz M, Detlefsen S, Esposito I, Friess H, Gress TM, Habisch HJ, et al: StellaTUM: Current consensus and discussion on pancreatic stellate cell research. Gut. 61:172–178. 2012. View Article : Google Scholar

17 

Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, et al: Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut. 62:112–120. 2013. View Article : Google Scholar :

18 

Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD and Hingorani SR: Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 21:418–429. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Charo C, Hwang RF, Arumugam T, Hwang R, Yang P, Dubois RN, Menter DG, Logsdon CD and Ramachandran V: Prostaglandin E2 regulates pancreatic stellate cell activity via the EP4 receptor. Pancreas. 42:467–474. 2013. View Article : Google Scholar :

20 

Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, et al: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 425:851–856. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN and Beachy PA: Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 425:846–851. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, et al: A paracrine requirement for hedgehog signalling in cancer. Nature. 455:406–410. 2008. View Article : Google Scholar : PubMed/NCBI

23 

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

24 

Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, Yoshimura A, Reindl W, Sipos B, Akira S, et al: Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 19:456–469. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Chang DZ, Ma Y, Ji B, Wang H, Deng D, Liu Y, Abbruzzese JL, Liu YJ, Logsdon CD and Hwu P: Mast cells in tumor micro-environment promotes the in vivo growth of pancreatic ductal adenocarcinoma. Clin Cancer Res. 17:7015–7023. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G and Bar-Sagi D: Oncogenic KRAS-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 21:836–847. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ and Vonderheide RH: Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 21:822–835. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Yadav D and Lowenfels AB: The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 144:1252–1261. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Pylayeva-Gupta Y, Grabocka E and Bar-Sagi D: RAS oncogenes: Weaving a tumorigenic web. Nat Rev Cancer. 11:761–774. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Steele CW, Jamieson NB, Evans TR, McKay CJ, Sansom OJ, Morton JP and Carter CR: Exploiting inflammation for therapeutic gain in pancreatic cancer. Br J Cancer. 108:997–1003. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Guerra C, Schuhmacher AJ, Cañamero M, Grippo PJ, Verdaguer L, Pérez-Gallego L, Dubus P, Sandgren EP and Barbacid M: Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 11:291–302. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Collins MA, Bednar F, Zhang Y, Brisset JC, Galbán S, Galbán CJ, Rakshit S, Flannagan KS, Adsay NV and Pasca di Magliano M: Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest. 122:639–653. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

34 

Feldmann G, Beaty R, Hruban RH and Maitra A: Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg. 14:224–232. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, Alberghina L, Stephanopoulos G and Chiaradonna F: Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol. 7:5232011. View Article : Google Scholar : PubMed/NCBI

36 

Dell'Antone P: Energy metabolism in cancer cells: How to explain the Warburg and Crabtree effects? Med Hypotheses. 79:388–392. 2012. View Article : Google Scholar

37 

Bryant KL, Mancias JD, Kimmelman AC and Der CJ: KRAS: Feeding pancreatic cancer proliferation. Trends Biochem Sci. 39:91–100. 2014. View Article : Google Scholar : PubMed/NCBI

38 

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

39 

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

40 

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

41 

Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, Au A, Rai TS, Zheng L, Ridgway R, et al: p53 status determines the role of autophagy in pancreatic tumour development. Nature. 504:296–300. 2013. View Article : Google Scholar : PubMed/NCBI

42 

Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB and Rabinowitz JD: Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci USA. 110:8882–8887. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, Grabocka E, Nofal M, Drebin JA, Thompson CB, et al: Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature. 497:633–637. 2013. View Article : Google Scholar : PubMed/NCBI

44 

Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, Lolkema MP, Buchholz M, Olive KP, Gress TM and Tuveson DA: Stromal biology and therapy in pancreatic cancer. Gut. 60:861–868. 2011. View Article : Google Scholar

45 

Zhu L, Shi G, Schmidt CM, Hruban RH and Konieczny SF: Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol. 171:263–273. 2007. View Article : Google Scholar : PubMed/NCBI

46 

Mazur PK and Siveke JT: Genetically engineered mouse models of pancreatic cancer: Unravelling tumour biology and progressin translational oncology. Gut. 61:1488–1500. 2012. View Article : Google Scholar

47 

Pérez-Mancera PA, Guerra C, Barbacid M and Tuveson DA: What we have learned about pancreatic cancer from mouse models. Gastroenterology. 142:1079–1092. 2012. View Article : Google Scholar : PubMed/NCBI

48 

Qiu W and Su GH: Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis. Cancer Metastasis Rev. 32:83–107. 2013. View Article : Google Scholar

49 

Westphalen CB and Olive KP: Genetically engineered mouse models of pancreatic cancer. Cancer J. 18:502–510. 2012. View Article : Google Scholar : PubMed/NCBI

50 

Hanlon L, Avila JL, Demarest RM, Troutman S, Allen M, Ratti F, Rustgi AK, Stanger BZ, Radtke F, Adsay V, et al: Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 70:4280–4286. 2010. View Article : Google Scholar : PubMed/NCBI

51 

Mazur PK, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, Zimber-Strobl U, Strobl LJ, Radtke F, Klöppel G, et al: Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 107:13438–13443. 2010. View Article : Google Scholar : PubMed/NCBI

52 

Guerra C, Collado M, Navas C, Schuhmacher AJ, Hernández-Porras I, Cañamero M, Rodriguez-Justo M, Serrano M and Barbacid M: Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene induced senescence. Cancer Cell. 19:728–739. 2011. View Article : Google Scholar : PubMed/NCBI

53 

Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, et al: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 321:1801–1806. 2008. View Article : Google Scholar : PubMed/NCBI

54 

Collisson EA, Trejo CL, Silva JM, Gu S, Korkola JE, Heiser LM, Charles RP, Rabinovich BA, Hann B, Dankort D, et al: A central role for RAF-MEK-ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov. 2:685–693. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Hruban RH, Canto M, Goggins M, Schulick R and Klein AP: Update on familial pancreatic cancer. Adv Surg. 44:293–311. 2010. View Article : Google Scholar : PubMed/NCBI

56 

Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, Karreth FA, Lim M, Barber LM, Clatworthy SA, et al: Germline Brca2 heterozygosity promotes Kras (G12D)-driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 18:499–509. 2010. View Article : Google Scholar : PubMed/NCBI

57 

Rowley M, Ohashi A, Mondal G, Mills L, Yang L, Zhang L, Sundsbak R, Shapiro V, Muders MH, Smyrk T and Couch FJ: Inactivation of Brca2 promotes Trp53-associated but inhibits KrasG12D-dependent pancreatic cancer development in mice. Gastroenterology. 140:1303–1313. e1–e3. 2011. View Article : Google Scholar : PubMed/NCBI

58 

Morton JP, Jamieson NB, Karim SA, Athineos D, Ridgway RA, Nixon C, McKay CJ, Carter R, Brunton VG, Frame MC, et al: LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 139:586–597. e1–e6. 2010. View Article : Google Scholar : PubMed/NCBI

59 

Hanahan D: Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 315:115–122. 1985. View Article : Google Scholar : PubMed/NCBI

60 

Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, Hezel AF, Horner J, Lauwers GY, Hanahan D and DePinho RA: Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 20:3130–3146. 2006. View Article : Google Scholar : PubMed/NCBI

61 

Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, Deng CX, Hruban RH, Adsay NV, Tuveson DA and Hingorani SR: Kras (G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 11:229–243. 2007. View Article : Google Scholar : PubMed/NCBI

62 

Siveke JT, Lubeseder-Martellato C, Lee M, Mazur PK, Nakhai H, Radtke F and Schmid RM: Notch signaling is required for exocrine regeneration after acute pancreatitis. Gastroenterology. 134:544–555. 2008. View Article : Google Scholar : PubMed/NCBI

63 

Vincent DF, Yan KP, Treilleux I, Gay F, Arfi V, Kaniewski B, Marie JC, Lepinasse F, Martel S, Goddard-Leon S, et al: Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet. 5:e10005752009. View Article : Google Scholar : PubMed/NCBI

64 

Appels NM, Beijnen JH and Schellens JH: Development of farnesyl transferase inhibitors: A review. Oncologist. 10:565–578. 2005. View Article : Google Scholar : PubMed/NCBI

65 

Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ, Giuliani EA, Gomez RP, Graham SL, Hamilton K, et al: Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med. 1:792–797. 1995. View Article : Google Scholar : PubMed/NCBI

66 

Whyte DB, Kirschmeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ, Bishop WR and Pai JK: K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem. 272:14459–14464. 1997. View Article : Google Scholar : PubMed/NCBI

67 

Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI and Waldmann H: Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling. Nature. 497:638–642. 2013. View Article : Google Scholar : PubMed/NCBI

68 

Chandra A, Grecco HE, Pisupati V, Perera D, Cassidy L, Skoulidis F, Ismail SA, Hedberg C, Hanzal-Bayer M, Venkitaraman AR, et al: The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol. 14:148–158. 2011. View Article : Google Scholar : PubMed/NCBI

69 

Weisz B, Giehl K, Gana-Weisz M, Egozi Y, Ben-Baruch G, Marciano D, Gierschik P and Kloog Y: A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice. Oncogene. 18:2579–2588. 1999. View Article : Google Scholar : PubMed/NCBI

70 

Laheru D, Shah P, Rajeshkumar NV, McAllister F, Taylor G, Goldsweig H, Le DT, Donehower R, Jimeno A, Linden S, et al: Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer. Invest New Drugs. 30:2391–2399. 2012. View Article : Google Scholar : PubMed/NCBI

71 

Patgiri A, Yadav KK, Arora PS and Bar-Sagi D: An orthosteric inhibitor of the Ras-Sos interaction. Nat Chem Biol. 7:585–587. 2011. View Article : Google Scholar : PubMed/NCBI

72 

Eser S, Reiff N, Messer M, Seidler B, Gottschalk K, Dobler M, Hieber M, Arbeiter A, Klein S, Kong B, et al: Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer. Cancer Cell. 23:406–420. 2013. View Article : Google Scholar : PubMed/NCBI

73 

Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI

74 

Shimizu T, Tolcher AW, Papadopoulos KP, Beeram M, Rasco DW, Smith LS, Gunn S, Smetzer L, Mays TA, Kaiser B, et al: The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin Cancer Res. 18:2316–2325. 2012. View Article : Google Scholar : PubMed/NCBI

75 

Molina-Arcas M, Hancock DC, Sheridan C, Kumar MS and Downward J: Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer. Cancer Discov. 3:548–563. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Ji S, Liang C, Qin Y, Jin K, Liang D, Xu W, Shi S, Zhang B, Liu L, Liu L, et al: Critical role of oncogenic KRAS in pancreatic cancer (Review). Mol Med Rep 13: 4943-4949, 2016.
APA
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D. ... Yu, X. (2016). Critical role of oncogenic KRAS in pancreatic cancer (Review). Molecular Medicine Reports, 13, 4943-4949. https://doi.org/10.3892/mmr.2016.5196
MLA
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D., Xu, W., Shi, S., Zhang, B., Liu, L., Liu, C., Xu, J., Ni, Q., Yu, X."Critical role of oncogenic KRAS in pancreatic cancer (Review)". Molecular Medicine Reports 13.6 (2016): 4943-4949.
Chicago
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D., Xu, W., Shi, S., Zhang, B., Liu, L., Liu, C., Xu, J., Ni, Q., Yu, X."Critical role of oncogenic KRAS in pancreatic cancer (Review)". Molecular Medicine Reports 13, no. 6 (2016): 4943-4949. https://doi.org/10.3892/mmr.2016.5196
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Ji S, Liang C, Qin Y, Jin K, Liang D, Xu W, Shi S, Zhang B, Liu L, Liu L, et al: Critical role of oncogenic KRAS in pancreatic cancer (Review). Mol Med Rep 13: 4943-4949, 2016.
APA
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D. ... Yu, X. (2016). Critical role of oncogenic KRAS in pancreatic cancer (Review). Molecular Medicine Reports, 13, 4943-4949. https://doi.org/10.3892/mmr.2016.5196
MLA
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D., Xu, W., Shi, S., Zhang, B., Liu, L., Liu, C., Xu, J., Ni, Q., Yu, X."Critical role of oncogenic KRAS in pancreatic cancer (Review)". Molecular Medicine Reports 13.6 (2016): 4943-4949.
Chicago
Liu, J., Ji, S., Liang, C., Qin, Y., Jin, K., Liang, D., Xu, W., Shi, S., Zhang, B., Liu, L., Liu, C., Xu, J., Ni, Q., Yu, X."Critical role of oncogenic KRAS in pancreatic cancer (Review)". Molecular Medicine Reports 13, no. 6 (2016): 4943-4949. https://doi.org/10.3892/mmr.2016.5196
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