Abstract
Drug resistance is a serious impediment to the treatment of cancer. The use of anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies in patients with metastatic colorectal cancer is guided by the presence of activating point mutations in KRAS and NRAS genes in the primary tumour. However, RAS wild-type status is still not sufficient to guarantee response to cetuximab and panitumumab, with response rates limited to 70% for combinations with multidrug chemotherapy. Therefore, additional mechanisms contributing to resistance are currently under investigation, and include genetic alterations and epigenetic mechanisms of resistance. In this regard, deregulation of miRNA expression profiles holds potential to unveil resistance and fuel the development of miRNA-based strategies to overcome EGFR-directed therapy limitations. We discuss current understanding of miRNA impact as modulators of EGFR therapy in patients with metastatic colorectal cancer and the future challenge of miRNAs in circulation as powerful non-invasive tools to monitor anti-EGFR therapy response and predict resistance.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adem BF, Bastos NR, Dias F, Teixeira AL, Medeiros R (2016) miRNAs: mediators of ErbB family targeted therapy resistance. Pharmacogenomics 17(10):1175–1187. https://doi.org/10.2217/pgs-2016-0038
Akao Y, Nakagawa Y, Naoe T (2006a) let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull 29(5):903–906. https://doi.org/10.1248/bpb.29.903
Akao Y, Nakagawa Y, Naoe T (2006b) MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep 16(4):845–850. https://doi.org/10.3892/or.16.4.845
Alam KJ, Mo JS, Han SH, Park WC, Kim HS, Yun KJ, Chae SC (2017) MicroRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the CTGF-EGFR signaling pathway. Int J Cancer 141(8):1614–1629. https://doi.org/10.1002/ijc.30861
Allen KE, Weiss GJ (2010) Resistance may not be futile: microRNA biomarkers for chemoresistance and potential therapeutics. Mol Cancer Ther 9(12):3126–3136. https://doi.org/10.1158/1535-7163.MCT-10-0397
Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634. https://doi.org/10.1200/JCO.2007.14.7116
Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108(12):5003–5008. https://doi.org/10.1073/pnas.1019055108
Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28(7):1254–1261. https://doi.org/10.1200/JCO.2009.24.6116
Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, Sartore-Bianchi A, Scala E et al (2013) Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov 3(6):658–673. https://doi.org/10.1158/2159-8290.CD-12-0558
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297. https://doi.org/10.1016/S0092-8674(04)00045-5
Biswas S, Rao CM (2017) Epigenetics in cancer: fundamentals and beyond. Pharmacol Ther 173:118–134. https://doi.org/10.1016/j.pharmthera.2017.02.011
Boisen MK, Dehlendorff C, Linnemann D, Nielsen BS, Larsen JS, Osterlind K, Nielsen SE, Tarpgaard LS et al (2014) Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab. PLoS One 9(10):e109430. https://doi.org/10.1371/journal.pone.0109430
Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671. https://doi.org/10.1200/JCO.2008.20.8397
Cappuzzo F, Sacconi A, Landi L, Ludovini V, Biagioni F, D’Incecco A, Capodanno A, Salvini J et al. (2014) MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies. Clin Colorectal Cancer 13(1):37–45 e34. doi: https://doi.org/10.1016/j.clcc.2013.11.006
Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee SS (2017) Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Mol Ther Nucleic Acids 8:132–143. https://doi.org/10.1016/j.omtn.2017.06.005
Chao CC, Wu PH, Huang HC, Chung HY, Chou YC, Cai BH, Kannagi R (2017) Downregulation of miR-199a/b-5p is associated with GCNT2 induction upon epithelial-mesenchymal transition in colon cancer. FEBS Lett 591(13):1902–1917. https://doi.org/10.1002/1873-3468.12685
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006. https://doi.org/10.1038/cr.2008.282
Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y, Cai X, Wang K et al (2009) Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene 28(10):1385–1392. https://doi.org/10.1038/onc.2008.474
Chen J, Wang W, Zhang Y, Chen Y, Hu T (2014a) Predicting distant metastasis and chemoresistance using plasma miRNAs. Med Oncol 31(1):799. https://doi.org/10.1007/s12032-013-0799-x
Chen P, Xi Q, Wang Q, Wei P (2014b) Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in colorectal cancer. Med Oncol 31(10):235. https://doi.org/10.1007/s12032-014-0235-x
Chou YT, Lin HH, Lien YC, Wang YH, Hong CF, Kao YR, Lin SC, Chang YC et al (2010) EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF. Cancer Res 70(21):8822–8831. https://doi.org/10.1158/0008-5472.CAN-10-0638
Cohenuram M, Saif MW (2007) Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anti-Cancer Drugs 18(1):7–15. https://doi.org/10.1097/CAD.0b013e32800feecb
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345. https://doi.org/10.1056/NEJMoa033025
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V et al (2010a) Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 11(8):753–762. https://doi.org/10.1016/S1470-2045(10)70130-3
De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S et al (2010b) Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304(16):1812–1820. https://doi.org/10.1001/jama.2010.1535
Della Vittoria Scarpati G, Falcetta F, Carlomagno C, Ubezio P, Marchini S, De Stefano A, Singh VK, D’Incalci M et al (2012) A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 83(4):1113–1119. https://doi.org/10.1016/j.ijrobp.2011.09.030
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28(31):4697–4705. https://doi.org/10.1200/JCO.2009.27.4860
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369(11):1023–1034. https://doi.org/10.1056/NEJMoa1305275
Earle JS, Luthra R, Romans A, Abraham R, Ensor J, Yao H, Hamilton SR (2010) Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma. J Mol Diagn 12(4):433–440. https://doi.org/10.2353/jmoldx.2010.090154
El Sharawy A, Roder C, Becker T, Habermann JK, Schreiber S, Rosenstiel P, Kalthoff H (2016) Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations. Oncotarget 7(46):75353–75365. https://doi.org/10.18632/oncotarget.12205
Ferracin M, Negrini M (2015) Micromarkers 2.0: an update on the role of microRNAs in cancer diagnosis and prognosis. Expert Rev Mol Diagn 15(10):1369–1381. https://doi.org/10.1586/14737159.2015.1081058
Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, Camponovo A, Etienne LL et al (2007) PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 97(8):1139–1145. https://doi.org/10.1038/sj.bjc.6604009
Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105. https://doi.org/10.1101/gr.082701.108
Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F et al (2011) EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med 18(1):74–82. https://doi.org/10.1038/nm.2577
Gomes SE, Simoes AE, Pereira DM, Castro RE, Rodrigues CM, Borralho PM (2016) miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells. Oncotarget 7(8):9368–9387. https://doi.org/10.18632/oncotarget.7010
Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J, Su F, Yao H et al (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286(21):19127–19137. https://doi.org/10.1074/jbc.M110.216887
Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, Warnecke JM, Sczakiel G (2010) A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol 28(6):655–661. https://doi.org/10.1016/j.urolonc.2009.01.027
Harding J, Burtness B (2005) Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Today (Barc) 41(2):107–127. https://doi.org/10.1358/dot.2005.41.2.882662
Heinemann V, Rivera F, O’Neil BH, Stintzing S, Koukakis R, Terwey JH, Douillard JY (2016) A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer 67:11–20. https://doi.org/10.1016/j.ejca.2016.07.019
Hu T, Li C (2010) Convergence between Wnt-beta-catenin and EGFR signaling in cancer. Mol Cancer 9:236. https://doi.org/10.1186/1476-4598-9-236
Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3(11):e3694. https://doi.org/10.1371/journal.pone.0003694
Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A (2011) MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res 71(15):5214–5224. https://doi.org/10.1158/0008-5472.CAN-10-4645
Igarashi H, Kurihara H, Mitsuhashi K, Ito M, Okuda H, Kanno S, Naito T, Yoshii S et al (2015) Association of microRNA-31-5p with clinical efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer. Ann Surg Oncol 22(8):2640–2648. https://doi.org/10.1245/s10434-014-4264-7
Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765. https://doi.org/10.1056/NEJMoa0804385
Kedmi M, Sas-Chen A, Yarden Y (2015) MicroRNAs and growth factors: an Alliance propelling tumor progression. J Clin Med 4(8):1578–1599. https://doi.org/10.3390/jcm4081578
Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD et al (2010) Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 24(24):2754–2759. https://doi.org/10.1101/gad.1950610
Kent OA, Fox-Talbot K, Halushka MK (2013) RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets. Oncogene 32(20):2576–2585. https://doi.org/10.1038/onc.2012.266
Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K (2007) Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 98(8):1275–1280. https://doi.org/10.1111/j.1349-7006.2007.00510.x
Kjersem JB, Ikdahl T, Lingjaerde OC, Guren T, Tveit KM, Kure EH (2014) Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatin-based treatment. Mol Oncol 8(1):59–67. https://doi.org/10.1016/j.molonc.2013.09.001
Kopp F, Wagner E, Roidl A (2014) The proto-oncogene KRAS is targeted by miR-200c. Oncotarget 5(1):185–195. https://doi.org/10.18632/oncotarget.1427
Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610. https://doi.org/10.1038/nrg2843
Lam JK, Chow MY, Zhang Y, Leung SW (2015) siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids 4:e252. https://doi.org/10.1038/mtna.2015.23
Lanza G, Ferracin M, Gafa R, Veronese A, Spizzo R, Pichiorri F, Liu CG, Calin GA et al (2007) mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer 6:54. https://doi.org/10.1186/1476-4598-6-54
Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134. https://doi.org/10.1016/j.cell.2010.06.011
Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Cote JF, Tomasic G et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66(8):3992–3995. https://doi.org/10.1158/0008-5472.CAN-06-0191
Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15(6):321–333. https://doi.org/10.1038/nrc3932
Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z, Singh B, Franklin JL et al (2017) lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/beta-catenin signaling. Nat Med 23(11):1331–1341. https://doi.org/10.1038/nm.4424
Luraghi P, Bigatto V, Cipriano E, Reato G, Orzan F, Sassi F, De Bacco F, Isella C et al (2018) A molecularly annotated model of patient-derived colon cancer stem-like cells to assess genetic and nongenetic mechanisms of resistance to anti-EGFR therapy. Clin Cancer Res 24(4):807–820. https://doi.org/10.1158/1078-0432.CCR-17-2151
Manceau G, Imbeaud S, Thiebaut R, Liebaert F, Fontaine K, Rousseau F, Genin B, Le Corre D et al (2014) Hsa-miR-31-3p expression is linked to progression-free survival in patients with KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy. Clin Cancer Res 20(12):3338–3347. https://doi.org/10.1158/1078-0432.CCR-13-2750
Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F (2009) Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol 158(1):1–9. https://doi.org/10.1111/j.1365-2249.2009.03992.x
Mekenkamp LJ, Tol J, Dijkstra JR, de Krijger I, Vink-Borger ME, van Vliet S, Teerenstra S, Kamping E et al (2012) Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients. BMC Cancer 12:292. https://doi.org/10.1186/1471-2407-12-292
Mellor JD, Brown MP, Irving HR, Zalcberg JR, Dobrovic A (2013) A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer. J Hematol Oncol 6:1. https://doi.org/10.1186/1756-8722-6-1
Migliore C, Giordano S (2013) Resistance to targeted therapies: a role for microRNAs? Trends Mol Med 19(10):633–642. https://doi.org/10.1016/j.molmed.2013.08.002
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518. https://doi.org/10.1073/pnas.0804549105
Mlcochova J, Faltejskova P, Nemecek R, Svoboda M, Slaby O (2013) MicroRNAs targeting EGFR signalling pathway in colorectal cancer. J Cancer Res Clin Oncol 139(10):1615–1624. https://doi.org/10.1007/s00432-013-1470-9
Mlcochova J, Faltejskova-Vychytilova P, Ferracin M, Zagatti B, Radova L, Svoboda M, Nemecek R, John S et al (2015) MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab. Oncotarget 6(36):38695–38704. https://doi.org/10.18632/oncotarget.5735
Mosakhani N, Lahti L, Borze I, Karjalainen-Lindsberg ML, Sundstrom J, Ristamaki R, Osterlund P, Knuutila S et al (2012a) MicroRNA profiling predicts survival in anti-EGFR treated chemorefractory metastatic colorectal cancer patients with wild-type KRAS and BRAF. Cancer Genet 205(11):545–551. https://doi.org/10.1016/j.cancergen.2012.08.003
Mosakhani N, Sarhadi VK, Borze I, Karjalainen-Lindsberg ML, Sundstrom J, Ristamaki R, Osterlund P, Knuutila S (2012b) MicroRNA profiling differentiates colorectal cancer according to KRAS status. Genes Chromosom Cancer 51(1):1–9. https://doi.org/10.1002/gcc.20925
Mussnich P, Rosa R, Bianco R, Fusco A, D’Angelo D (2015) MiR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1. Expert Opin Ther Targets 19(8):1017–1026. https://doi.org/10.1517/14728222.2015.1057569
Nakagawa Y, Akao Y, Taniguchi K, Kamatani A, Tahara T, Kamano T, Nakano N, Komura N et al (2015) Relationship between expression of onco-related miRNAs and the endoscopic appearance of colorectal tumors. Int J Mol Sci 16(1):1526–1543. https://doi.org/10.3390/ijms16011526
Oberg AL, French AJ, Sarver AL, Subramanian S, Morlan BW, Riska SM, Borralho PM, Cunningham JM et al (2011) miRNA expression in colon polyps provides evidence for a multihit model of colon cancer. PLoS One 6(6):e20465. https://doi.org/10.1371/journal.pone.0020465
Pagliuca A, Valvo C, Fabrizi E, di Martino S, Biffoni M, Runci D, Forte S, De Maria R et al (2013) Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. Oncogene 32(40):4806–4813. https://doi.org/10.1038/onc.2012.495
Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT (2009) Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 15(17):5473–5477. https://doi.org/10.1158/1078-0432.CCR-09-0736
Pasquinelli AE (2012) MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 13(4):271–282. https://doi.org/10.1038/nrg3162
Pekow JR, Dougherty U, Mustafi R, Zhu H, Kocherginsky M, Rubin DT, Hanauer SB, Hart J et al (2012) miR-143 and miR-145 are downregulated in ulcerative colitis: putative regulators of inflammation and protooncogenes. Inflamm Bowel Dis 18(1):94–100. https://doi.org/10.1002/ibd.21742
Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM (2013) Delivering the promise of miRNA cancer therapeutics. Drug Discov Today 18(5–6):282–289. https://doi.org/10.1016/j.drudis.2012.10.002
Perkins G, Pilati C, Blons H, Laurent-Puig P (2014) Beyond KRAS status and response to anti-EGFR therapy in metastatic colorectal cancer. Pharmacogenomics 15(7):1043–1052. https://doi.org/10.2217/pgs.14.66
Pichler M, Winter E, Ress AL, Bauernhofer T, Gerger A, Kiesslich T, Lax S, Samonigg H et al (2014) miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor. J Clin Pathol 67(3):198–203. https://doi.org/10.1136/jclinpath-2013-201904
Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S et al (2016) Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer 68:51–59. https://doi.org/10.1016/j.ejca.2016.08.010
Pugh S, Thiebaut R, Bridgewater J, Grisoni ML, Moutasim K, Rousseau F, Thomas GJ, Griffiths G et al (2017) Association between miR-31-3p expression and cetuximab efficacy in patients with KRAS wild-type metastatic colorectal cancer: a post-hoc analysis of the New EPOC trial. Oncotarget 8(55):93856–93866. https://doi.org/10.18632/oncotarget.21291
Ragusa M, Majorana A, Statello L, Maugeri M, Salito L, Barbagallo D, Guglielmino MR, Duro LR et al (2010) Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment. Mol Cancer Ther 9(12):3396–3409. https://doi.org/10.1158/1535-7163.MCT-10-0137
Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16(3):203–222. https://doi.org/10.1038/nrd.2016.246
Rupaimoole R, Calin GA, Lopez-Berestein G, Sood AK (2016) miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov 6(3):235–246. https://doi.org/10.1158/2159-8290.CD-15-0893
Ruzzo A, Graziano F, Vincenzi B, Canestrari E, Perrone G, Galluccio N, Catalano V, Loupakis F et al (2012) High let-7a microRNA levels in KRAS-mutated colorectal carcinomas may rescue anti-EGFR therapy effects in patients with chemotherapy-refractory metastatic disease. Oncologist 17(6):823–829. https://doi.org/10.1634/theoncologist.2012-0081
Salgia R, Kulkarni P (2018) The genetic/non-genetic duality of drug ‘Resistance’ in cancer. Trends Cancer 4(2):110–118. https://doi.org/10.1016/j.trecan.2018.01.001
Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P et al (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69(5):1851–1857. https://doi.org/10.1158/0008-5472.CAN-08-2466
Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KA, Morlan BW, Riska SM et al (2009) Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9:401. https://doi.org/10.1186/1471-2407-9-401
Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjot L, Wiuf C, Sorensen FJ et al (2008) Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 68(15):6416–6424. https://doi.org/10.1158/0008-5472.CAN-07-6110
Schetter AJ, Okayama H, Harris CC (2012) The role of microRNAs in colorectal cancer. Cancer J 18(3):244–252. https://doi.org/10.1097/PPO.0b013e318258b78f
Schou JV, Rossi S, Jensen BV, Nielsen DL, Pfeiffer P, Hogdall E, Yilmaz M, Tejpar S et al (2014) miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan. PLoS One 9(6):e99886. https://doi.org/10.1371/journal.pone.0099886
Schwarzenbach H, Nishida N, Calin GA, Pantel K (2014) Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol 11(3):145–156. https://doi.org/10.1038/nrclinonc.2014.5
Sethupathy P, Collins FS (2008) MicroRNA target site polymorphisms and human disease. Trends Genet 24(10):489–497. https://doi.org/10.1016/j.tig.2008.07.004
Seviour EG, Sehgal V, Mishra D, Rupaimoole R, Rodriguez-Aguayo C, Lopez-Berestein G, Lee JS, Sood AK et al (2017) Targeting KRas-dependent tumour growth, circulating tumour cells and metastasis in vivo by clinically significant miR-193a-3p. Oncogene 36(10):1339–1350. https://doi.org/10.1038/onc.2016.308
Sha D, Lee AM, Shi Q, Alberts SR, Sargent DJ, Sinicrope FA, Diasio RB (2014) Association study of the let-7 miRNA-complementary site variant in the 3′ untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial). Clin Cancer Res 20(12):3319–3327. https://doi.org/10.1158/1078-0432.CCR-14-0069
Shigeyasu K, Toden S, Zumwalt TJ, Okugawa Y, Goel A (2017) Emerging role of microRNAs as liquid biopsy biomarkers in gastrointestinal cancers. Clin Cancer Res 23(10):2391–2399. https://doi.org/10.1158/1078-0432.CCR-16-1676
Slattery ML, Wolff E, Hoffman MD, Pellatt DF, Milash B, Wolff RK (2011) MicroRNAs and colon and rectal cancer: differential expression by tumor location and subtype. Genes Chromosomes Cancer 50(3):196–206. https://doi.org/10.1002/gcc.20844
Slattery ML, Herrick JS, Mullany LE, Wolff E, Hoffman MD, Pellatt DF, Stevens JR, Wolff RK (2016a) Colorectal tumor molecular phenotype and miRNA: expression profiles and prognosis. Mod Pathol 29(8):915–927. https://doi.org/10.1038/modpathol.2016.73
Slattery ML, Herrick JS, Pellatt DF, Stevens JR, Mullany LE, Wolff E, Hoffman MD, Samowitz WS et al (2016b) MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression. Carcinogenesis 37(3):245–261. https://doi.org/10.1093/carcin/bgv249
Spano JP, Lagorce C, Atlan D, Milano G, Domont J, Benamouzig R, Attar A, Benichou J et al (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16(1):102–108. https://doi.org/10.1093/annonc/mdi006
Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U et al (2016) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol 17(10):1426–1434. https://doi.org/10.1016/S1470-2045(16)30269-8
Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, Li J (2012) Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One 7(10):e47003. https://doi.org/10.1371/journal.pone.0047003
Suto T, Yokobori T, Yajima R, Morita H, Fujii T, Yamaguchi S, Altan B, Tsutsumi S et al (2015) MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation. Carcinogenesis 36(3):338–345. https://doi.org/10.1093/carcin/bgu242
Svoboda M, Sana J, Fabian P, Kocakova I, Gombosova J, Nekvindova J, Radova L, Vyzula R et al (2012) MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients. Radiat Oncol 7:195. https://doi.org/10.1186/1748-717X-7-195
Svoronos AA, Engelman DM, Slack FJ (2016) OncomiR or tumor suppressor? the duplicity of microRNAs in cancer. Cancer Res 76(13):3666–3670. https://doi.org/10.1158/0008-5472.CAN-16-0359
Takahashi H, Takahashi M, Ohnuma S, Unno M, Yoshino Y, Ouchi K, Takahashi S, Yamada Y et al (2017) microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer. BMC Cancer 17(1):723. https://doi.org/10.1186/s12885-017-3739-x
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. https://doi.org/10.1038/ncb1596
Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664. https://doi.org/10.1200/JCO.2006.08.1620
Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13(4):423–433. https://doi.org/10.1038/ncb2210
Vidigal JA, Ventura A (2015) The biological functions of miRNAs: lessons from in vivo studies. Trends Cell Biol 25(3):137–147. https://doi.org/10.1016/j.tcb.2014.11.004
Wang Y, Tang Q, Li M, Jiang S, Wang X (2014) MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun 444(2):199–204. https://doi.org/10.1016/j.bbrc.2014.01.028
Waring P, Tie J, Maru D, Karapetis CS (2016) RAS mutations as predictive biomarkers in clinical management of metastatic colorectal cancer. Clin Colorectal Cancer 15(2):95–103. https://doi.org/10.1016/j.clcc.2015.10.006
Witsch E, Sela M, Yarden Y (2010) Roles for growth factors in cancer progression. Physiology (Bethesda) 25(2):85–101. https://doi.org/10.1152/physiol.00045.2009
Witwer KW (2015) Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin Chem 61(1):56–63. https://doi.org/10.1373/clinchem.2014.221341
Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, Ju J (2007) Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 13(10):1668–1674. https://doi.org/10.1261/rna.642907
Zhang N, Li X, Wu CW, Dong Y, Cai M, Mok MT, Wang H, Chen J et al (2013) microRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis. Oncogene 32(42):5078–5088. https://doi.org/10.1038/onc.2012.526
Zhang J, Zhang K, Bi M, Jiao X, Zhang D, Dong Q (2014) Circulating microRNA expressions in colorectal cancer as predictors of response to chemotherapy. Anti-Cancer Drugs 25(3):346–352. https://doi.org/10.1097/CAD.0000000000000049
Zhang X, Ma X, An H, Xu C, Cao W, Yuan W, Ma J (2017) Upregulation of microRNA-125b by G-CSF promotes metastasis in colorectal cancer. Oncotarget 8(31):50642–50654. https://doi.org/10.18632/oncotarget.16892
Zhao B, Wang L, Qiu H, Zhang M, Sun L, Peng P, Yu Q, Yuan X (2017) Mechanisms of resistance to anti-EGFR therapy in colorectal cancer. Oncotarget 8(3):3980–4000. https://doi.org/10.18632/oncotarget.14012
Zhou J, Lv L, Lin C, Hu G, Guo Y, Wu M, Tian B, Li X (2015) Combinational treatment with microRNA133b and cetuximab has increased inhibitory effects on the growth and invasion of colorectal cancer cells by regulating EGFR. Mol Med Rep 12(4):5407–5414. https://doi.org/10.3892/mmr.2015.4046
Zhu H, Dougherty U, Robinson V, Mustafi R, Pekow J, Kupfer S, Li YC, Hart J et al (2011) EGFR signals downregulate tumor suppressors miR-143 and miR-145 in Western diet-promoted murine colon cancer: role of G1 regulators. Mol Cancer Res 9(7):960–975. https://doi.org/10.1158/1541-7786.MCR-10-0531
Zhu Y, Peng Q, Lin Y, Zou L, Shen P, Chen F, Min M, Shen L et al (2017) Identification of biomarker microRNAs for predicting the response of colorectal cancer to neoadjuvant chemoradiotherapy based on microRNA regulatory network. Oncotarget 8(2):2233–2248. https://doi.org/10.18632/oncotarget.13659
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Pereira, D.M., Rodrigues, C.M.P. (2018). miRNAs as Modulators of EGFR Therapy in Colorectal Cancer. In: Jordan, P. (eds) Targeted Therapy of Colorectal Cancer Subtypes. Advances in Experimental Medicine and Biology, vol 1110. Springer, Cham. https://doi.org/10.1007/978-3-030-02771-1_9
Download citation
DOI: https://doi.org/10.1007/978-3-030-02771-1_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-02770-4
Online ISBN: 978-3-030-02771-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)