title: Beyond KRAS: Predictive factors of the efficacy of anti-EGFR monoclonal antibodies in the treatment of metastatic colorectal cancer.
abstract: Systematic analysis of the epidermal growth factor receptor (EGFR) pathway revealed that biomarkers could be used to predict the response to and outcome of anti-EGFR therapies in patients affected by metastatic colorectal cancer. We have conducted a review on the most recent findings and advances on this topic. To this aim, we searched the PubMed database for articles devoted to predictive and prognostic biomarkers for patients administered cetuximab- and panitumumab-based therapies. Here we review the state of the art and the controversies about the molecular factors known to be predictors of the efficacy of anti-EGFR therapy, namely, KRAS, BRAF, NRAS, PI3KCA and PTEN, and we discuss their prognostic value in colorectal cancer patients.
authors.affiliation: Alfonso De Stefano, Chiara Carlomagno, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Stefano
authors.affiliation: Alfonso De Stefano, Chiara Carlomagno, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Anti-epidermal growth factor receptor; Biomarkers; KRAS; Metastatic colorectal cancer
references.citation: J R Soc Med. 2010 Feb;103(2):60-6
references.pmid: 20118336
references.citation: BMC Cancer. 2008 Aug 13;8:234
references.pmid: 18700047
references.citation: Lancet. 2011 Jun 18;377(9783):2103-14
references.pmid: 21641636
references.citation: Cancer Res. 2007 Mar 15;67(6):2643-8
references.pmid: 17363584
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: J Clin Oncol. 2011 Apr 1;29(10):1261-70
references.pmid: 21383284
references.citation: J Clin Oncol. 2013 Feb 20;31(6):759-65
references.pmid: 23182985
references.citation: Br J Cancer. 2008 Jul 8;99(1):83-9
references.pmid: 18577988
references.citation: J Clin Oncol. 2010 Nov 1;28(31):4706-13
references.pmid: 20921462
references.citation: J Clin Oncol. 2008 Dec 10;26(35):5705-12
references.pmid: 19001320
references.citation: J Clin Oncol. 2000 Aug;18(16):2938-47
references.pmid: 10944126
references.citation: Cancer Res. 2008 Mar 15;68(6):1953-61
references.pmid: 18339877
references.citation: N Engl J Med. 2009 Jul 2;361(1):98-9
references.pmid: 19571295
references.citation: Lancet. 2000 Mar 25;355(9209):1041-7
references.pmid: 10744089
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1254-61
references.pmid: 20100961
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: Cancer Res Treat. 2013 Mar;45(1):55-62
references.pmid: 23613671
references.citation: Lancet Oncol. 2010 Aug;11(8):753-62
references.pmid: 20619739
references.citation: N Engl J Med. 2008 Oct 23;359(17):1757-65
references.pmid: 18946061
references.citation: J Natl Cancer Inst. 2009 Oct 7;101(19):1308-24
references.pmid: 19738166
references.citation: Clin Cancer Res. 2009 May 1;15(9):3184-8
references.pmid: 19366826
references.citation: Cancer Res. 2009 Mar 1;69(5):1851-7
references.pmid: 19223544
references.citation: World J Gastroenterol. 2007 Jul 28;13(28):3806-15
references.pmid: 17657834
references.citation: Cancer Res. 2004 May 1;64(9):3014-21
references.pmid: 15126336
references.citation: J Clin Oncol. 2008 May 10;26(14):2311-9
references.pmid: 18390971
references.citation: J Clin Oncol. 2008 Apr 1;26(10):1626-34
references.pmid: 18316791
references.citation: Cancer. 1992 Sep 1;70(5 Suppl):1206-15
references.pmid: 1511368
references.citation: J Clin Oncol. 2005 Dec 20;23(36):9441-2
references.pmid: 16361649
references.citation: Br J Cancer. 2009 Apr 7;100(7):1087-94
references.pmid: 19293803
references.citation: J Cell Physiol. 2005 Aug;204(2):484-8
references.pmid: 15702478
references.citation: Ann Oncol. 2011 Jul;22(7):1535-1546
references.pmid: 21228335
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5924-30
references.pmid: 19884556
references.citation: J Pathol. 2004 Sep;204(1):65-74
references.pmid: 15307139
references.citation: Cancer Res. 2006 Apr 15;66(8):3992-5
references.pmid: 16618717
references.citation: J Clin Oncol. 2012 May 20;30(15):1755-62
references.pmid: 22473155
references.citation: Clin Colorectal Cancer. 2014 Mar;13(1):14-26.e1
references.pmid: 24370353
references.citation: J Clin Oncol. 2009 Jun 1;27(16):2622-9
references.pmid: 19398573
references.citation: Eur J Cancer. 2010 Jul;46(11):1997-2009
references.pmid: 20413299
references.citation: Int J Cancer. 2008 May 15;122(10):2255-9
references.pmid: 18224685
references.citation: Oncologist. 2008 Dec;13(12):1270-5
references.pmid: 19056857
references.citation: Clin Cancer Res. 2011 Jul 15;17(14):4901-14
references.pmid: 21632860
references.citation: J Clin Oncol. 1992 Jun;10(6):896-903
references.pmid: 1534121
references.citation: Nat Rev Cancer. 2006 Mar;6(3):184-92
references.pmid: 16453012
references.citation: Br J Cancer. 2001 Sep 1;85(5):692-6
references.pmid: 11531254
references.citation: J Clin Oncol. 2007 May 1;25(13):1658-64
references.pmid: 17470858
references.citation: Ann Surg. 2008 Jan;247(1):125-35
references.pmid: 18156932
references.citation: Lancet Oncol. 2010 Jan;11(1):38-47
references.pmid: 19942479
references.citation: PLoS One. 2009 Oct 02;4(10):e7287
references.pmid: 19806185
references.citation: J Clin Oncol. 2008 May 20;26(15):2600; author reply 2601-2
references.pmid: 18487581
references.citation: J Clin Oncol. 2011 May 20;29(15):2011-9
references.pmid: 21502544
references.citation: J Natl Cancer Inst. 1998 May 6;90(9):675-84
references.pmid: 9586664
references.citation: J Clin Oncol. 2010 Mar 1;28(7):e111-2
references.pmid: 20008635
references.citation: Cancer J. 2011 Mar-Apr;17(2):114-26
references.pmid: 21427555
references.citation: J Clin Oncol. 2011 Mar 10;29(8):1050-8
references.pmid: 21300933
references.citation: J Clin Oncol. 2008 Nov 20;26(33):5320-1
references.pmid: 18936470
references.citation: J Clin Oncol. 2008 Dec 10;26(35):5668-70
references.pmid: 19001346
references.citation: J Clin Oncol. 2010 Jan 20;28(3):466-74
references.pmid: 20008640
references.citation: Cell. 2000 Feb 18;100(4):387-90
references.pmid: 10693755
references.citation: J Clin Oncol. 2010 Oct 1;28(28):e529-31; author reply e532-e533
references.pmid: 20679615
references.citation: Eur J Cancer. 2005 Jul;41(11):1649-54
references.pmid: 15994075
references.citation: JAMA. 2010 Oct 27;304(16):1812-20
references.pmid: 20978259
references.citation: J Clin Oncol. 2009 Mar 20;27(9):1477-84
references.pmid: 19237633
references.citation: Br J Cancer. 2007 Oct 22;97(8):1035-9
references.pmid: 17895897
references.citation: Ann Oncol. 2008 Mar;19(3):508-15
references.pmid: 17998284
references.citation: World J Gastroenterol. 2012 Jan 7;18(1):25-33
references.pmid: 22228967
references.citation: Eur J Cancer. 2012 Jul;48(10):1466-75
references.pmid: 22446022
references.citation: J Clin Oncol. 2008 Jan 20;26(3):374-9
references.pmid: 18202412
references.citation: Lancet Oncol. 2005 May;6(5):279-86
references.pmid: 15863375
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: J Clin Oncol. 2009 Feb 10;27(5):663-71
references.pmid: 19114683
references.citation: J Clin Oncol. 2010 Nov 1;28(31):4697-705
references.pmid: 20921465
references.citation: Br J Cancer. 2007 Oct 22;97(8):1139-45
references.pmid: 17940504
references.citation: Pathology. 2008 Apr;40(3):295-8
references.pmid: 18428050
references.citation: Lancet Oncol. 2013 Jul;14(8):749-59
references.pmid: 23725851
references.citation: Cancer Treat Rev. 2009 May;35(3):262-71
references.pmid: 19117687
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5931-7
references.pmid: 19884549
references.citation: N Engl J Med. 2009 Feb 5;360(6):563-72
references.pmid: 19196673
references.citation: Gastrointest Cancer Res. 2009 Sep;3(5 Supplement 2):S15-22
references.pmid: 20011559
references.citation: Adv Clin Chem. 2010;51:71-119
references.pmid: 20857619
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Br J Cancer. 2009 Aug 18;101(4):715-21
references.pmid: 19603018
references.citation: J Clin Oncol. 2012 Oct 10;30(29):3570-7
references.pmid: 22734028
references.citation: N Engl J Med. 2013 Sep 12;369(11):1023-34
references.pmid: 24024839
references.citation: Ann Oncol. 2004 Jun;15(6):933-9
references.pmid: 15151951