Targeted therapies in colorectal cancer-an integrative view by pppm

EPMA Journal

Volumn 4, Issue 1, 2013, Pages

  Hagan, Suzanne ^a   M Orr, Maria C ^b   Doyle, Brendan ^c  

^a GLASGOW CALEDONIAN UNIVERSITY   (United Kingdom)

^b ASTRAZENECA   (United Kingdom)

^c ST JAMES S HOSPITAL   (Ireland)

Author keywords

Anti EGFR; Anti VEGF; Clinical decision making process; CRC management; Integrative medical approach; Molecularly targeted treatment; Monoclonal antibody therapy; Prediction; Therapy monitoring; Therapy response

Indexed keywords

B RAF KINASE; BEVACIZUMAB; CETUXIMAB; ERLOTINIB; FLUOROURACIL; GEFITINIB; K RAS PROTEIN; OXALIPLATIN; PANITUMUMAB; PAZOPANIB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SORAFENIB; SUNITINIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2;

ACNE; ANOREXIA; CANCER CLASSIFICATION; CANCER COMBINATION CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; COLORECTAL CANCER; DRUG CONTRAINDICATION; DRUG EFFECT; DRUG RESPONSE; DRUG SAFETY; DRUG TARGETING; GENE MUTATION; GENE OVEREXPRESSION; GENETIC POLYMORPHISM; HUMAN; HYPERTENSION; MOLECULARLY TARGETED THERAPY; NUCLEAR MAGNETIC RESONANCE IMAGING; ONCOGENE K RAS; PERSONALIZED MEDICINE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RASH; REVIEW; SKIN TOXICITY;

EID: 84994652568     PISSN: 18785077     EISSN: 18785085     Source Type: Journal    
DOI: 10.1186/1878-5085-4-3     Document Type: Review

References (146)

1. Ferlay J, Parkin DM, Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010, 46(4):765-781.
2. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, et al: The genomic landscapes of human breast and colorectal cancers. Science 2007, 318(5853):1108-1113.
3. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, et al: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008, 321(5897):1801-1806.
4. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, et al: An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321(5897):1807-1812.
5. Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, et al: Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 2012, 485(7399):502-506.
6. Wagle N, Berger MF, Davis MJ, Blumenstiel B, Defelice M, Pochanard P, Ducar M, Van Hummelen P, Macconaill LE, Hahn WC, Meyerson M, Gabriel SB, Garraway LA: High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov 2012, 2(1):82-93.
7. McBride DJ, Etemadmoghadam D, Australian Ovarian Cancer Study Group, Cooke SL, Alsop K, George J, Butler A, Cho J, Galappaththige D, Greenman C, Howarth KD, Lau KW, Ng CK, Raine K, Teague J, Wedge DC, Caubit X, Stratton MR, Brenton JD, Campbell PJ, Futreal PA, Bowtell DD: Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes. J Pathol 2012, 227(4):446-455.
8. Migliore L, Migheli F, Spisni R, Coppedè F: Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol 2011, 2011:792362.
9. Markman B, Javier Ramos F, Capdevila J, Tabernero J: EGFR and KRAS in colorectal cancer. Adv Clin Chem 2010, 51:71-119.
10. He J, Efron JE: Screening for colorectal cancer. Adv Surg 2011, 45:31-44.
11. Howlander N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (Eds): SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda: National Cancer Institute; 2012.
12. National Cancer Intelligence Network (NCIN): Data Briefing. Colorectal Cancer Survival by Stage. [http://www.ncin.org.uk/publications/data_briefings/colorectal_cancer_survival_by_stage.aspx]
13. Pino MS, Chung DC: Microsatellite instability in the management of colorectal cancer. Expert Rev Gastroenterol Hepatol 2011, 5(3):385-399.
14. Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F: Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010, 28(3):466-474.
15. Yamauchi M, Morikawa T, Kuchiba A, Imamura Y, Qian ZR, Nishihara R, Liao X, Waldron L, Hoshida Y, Huttenhower C, Chan AT, Giovannucci E, Fuchs C, Ogino S: Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 2012, 61(6):847-854.
16. Zlobec I, Bihl M, Foerster A, Rufle A, Lugli A: Comprehensive analysis of CpG island methylator phenotype (CIMP)-high,-low, and-negative colorectal cancers based on protein marker expression and molecular features. J Pathol 2011, 225(3):336-343.
17. Jass JR: Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007, 50(1):113-130.
18. Jover R, Nguyen TP, Pérez-Carbonell L, Zapater P, Payá A, Alenda C, Rojas E, Cubiella J, Balaguer F, Morillas JD, Clofent J, Bujanda L, Reñé JM, Bessa X, Xicola RM, Nicolás-Pérez D, Castells A, Andreu M, Llor X, Boland CR, Goel A: 5-fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology 2011, 140(4):1174-1181.
19. Des Guetz G, Uzzan B, Nicolas P, Schischmanoff O, Perret GY, Morere JF: Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer: a systematic review and meta-analysis. Anticancer Res 2009, 29(5):1615-1620.
20. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL: Genetic alterations during colorectal-tumor development. N Engl J Med 1988, 319(9):525-532.
21. Kobayashi H, Mochizuki H, Morita T, Kotake K, Teramoto T, Kameoka S, Saito Y, Takahashi K, Hase K, Oya M, Maeda K, Hirai T, Kameyama M, Shirouzu K, Sugihara K: Characteristics of recurrence after curative resection for T1 colorectal cancer: Japanese multicenter study. J Gastroenterol 2011, 46(2):203-211.
22. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Eng J Med 2004, 350:2335-2342.
23. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009, 360:1408-1417.
24. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Blasinska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J: 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 2010, 28:4697-4705.
25. Folkman J, Merler E, Abernathy C, Williams G: Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971, 133(2):275-288.
26. Samelis GF, Ekmektzoglou KA, Tsiakou A, Konstadoulakis M: The continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer offers a survival benefit. Hepatogastroenterology 2011, 58(112):1968-1971.
27. Guan ZZ, Xu JM, Luo RC, Feng FY, Wang LW, Shen L, Yu SY, Ba Y, Liang J, Wang D, Qin SK, Wang JJ, He J, Qi C, Xu RH: Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Chin J Cancer 2011, 30(10):682-689.
28. Zoratto F, Rossi L, Zullo A, Papa A, Zaccarelli E, Tomao L, Giordani E, Colonna M, Baiano G, Tomao S: Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer. Onco Targets Ther 2012, 5:199-211.
29. Hori N, Iwasa S, Hashimoto H, Yanai T, Kato K, Hamaguchi T, Yamada Y, Murakoshi K, Yokote N, Yamamoto H, Shimada Y: Reasons for avoidance of bevacizumab with first-line FOLFOX for advanced colorectal cancer. Int J Clin Oncol. doi:10.1007/s10147-012-0398-4.
30. Bonifazi M, Rossi M, Moja L, Scigliano VD, Franchi M, La Vecchia C, Zocchetti C, Negri E: Bevacizumab in clinical practice: prescribing appropriateness relative to national indications and safety. Oncologist 2012, 17(1):117-124.
31. Kabbinavar FF, Flynn PJ, Kozloff M, Ashby MA, Sing A, Barr CE, Grothey A: Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study. Eur J Cancer 2012, 48(8):1126-1132.
32. Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer WA, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008, 26(12):2013-2019.
33. Bergers G, Hanahan D: Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008, 8(8):592-603.
34. Leite De Oliveira R, Hamm A, Mazzone M: Growing tumor vessels: more than one way to skin a cat-implications for angiogenesis targeted cancer therapies. Mol Aspects Med 2011, 32(2):71-87.
35. Wozel G, Sticherling M, Schön MP: Cutaneous side effects of inhibition of VEGF signal transduction. J Dtsch Dermatol Ges 2010, 8(4):243-249.
36. Gotlib V, Khaled S, Lapko I, Mar N, Saif MW: Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response. Anticancer Drugs 2006, 17(10):1227-1229.
37. Saif MW, Longo WL, Israel G: Correlation between rash and a positive drug response associated with bevacizumab in a patient with advanced colorectal cancer. Clin Colorectal Cancer 2008, 7(2):144-148.
38. Manzoni M, Mariucci S, Delfanti S, Rovati B, Ronzoni M, Loupakis F, Brugnatelli S, Tinelli C, Villa E, Falcone A, Danova M: Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in bevacizumab-based treatment for advanced colorectal cancer. J Cancer Res Clin Oncol 2012, 138(7):1187-1196.
39. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, Clark JW, Abrams TA, Chan JA, Enzinger PC, Bhargava P, Kwak EL, Allen JN, Jain SR, Stuart K, Horgan K, Sheehan S, Fuchs CS, Ryan DP, Sahani DV: Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol 2010, 11:48-54.
40. Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, Satyamurthy N, Pope W, Lai A, Phelps ME, Cloughesy T: Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol 2007, 25:4714-4721.
41. Mrozek E, Lustberg MB, Knopp MV, Spigos DG, Yang X, Houton LA, Ramaswamy B, Layman RM, Povoski SP, Agnese DM: Phase II trial of neoadjuvant chemotherapy (NCT) with weekly nanoparticle albuminbound paclitaxel (Nab-P), carboplatin (CBP), and bevacizumab (BEV) in women with clinical stages II-III breast cancer (BC): pathologic response prediction by changes in angiogenic volume (AV) by dynamic contrast magnetic resonance imaging (DCE-MRI) [abstract]. J Clin Oncol 2010, 28:604.
42. Zweifel M, Padhani AR: Perfusion MRI in the early clinical development of antivascular drugs: decorations or decision making tools? Eur J Nucl Med Mol Imaging 2010, 37(Suppl 1):S164-S182.
43. O'Connor JPB, Rose CJ, Jackson A, Watson Y, Cheung S, Maders F, Whitcher BJ, Roberts C, Buonaccorsi GA, Thompson X, Clamp AR, Jayson GC, Parker GJM: DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6. Br J Cancer 2011, 105:139-145.
44. Syrigos KN, Karapanagiotou E, Boura P, Manegold C, Harrington K: Bevacizumab-induced hypertension: pathogenesis and management. BioDrugs 2011, 25(3):159-169.
45. Friberg G, Kasza K, Vokes EE, Kindler HL: Early hypertension (HTN) as a potential pharmacodynamic (PD) marker for survival in pancreatic cancer (PC) patients (pts) treated with bevacizumab (B) and gemcitabine (G) [abstract]. J Clin Oncol 2005, 23:3020.
46. Bono P, Elfving H, Utriainen T, Osterlund P, Saarto T, Alanko T, Joensuu H: Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol 2009, 20:393-394.
47. Scartozzi M, Galizia E, Chiorrini S, Giampieri R, Berardi R, Pierantoni C, Cascinu S: Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol 2009, 20:227-230.
48. Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD: Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 2008, 26:4672-4678.
49. Dahlberg SE, Sandler AB, Brahmer JR, Schiller JH, Johnson DH: Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J Clin Oncol 2010, 28:949-954.
50. Hurwitz H, Douglas PS, Middleton JP, Sledge GW, Johnson DH, Reardon DA, Chen D, Rosen O: Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV) [abstract]. J Clin Oncol 2010, 28:3039.
51. Dewdney A, Cunningham D, Barbachano Y, Chau I: Correlation of bevacizumab-induced hypertension and outcome in the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liveronly metastases unsuitable for upfront resection. Br J Cancer 2012, 106(11):1718-1721.
52. Bernaards C, Hegde P, Chen D, Holmgren E, Zheng M, Jubb AM, Koeppen H, Scherer SJ, Chen DS: Circulating vascular endothelial growth factor (VEGF) as a biomarker for bevacizumab-based therapy in metastatic colorectal, non-small cell lung, and renal cell cancers: analysis of phase III studies. J Clin Oncol 2010, 28:15s(suppl; abstr 10519).
53. Duda DG, Willett CG, Ancukiewicz M, di Tomaso E, Shah M, Czito BG, Bentley R, Poleski M, Lauwers GY, Carroll M, Tyler D, Mantyh C, Shellito P, Clark JW, Jain RK: Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer. Oncologist 2010, 15:577-583.
54. Jubb AM, Harris AL: Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol 2010, 11:1172-1183.
55. Wilson PM, Labonte MJ, Lenz HJ: Assessing the in vivo efficacy of biologic antiangiogenic therapies. Cancer Chemother Pharmacol 2012, 12(6):468-475.
56. Abajo A, Boni V, Lopez I, Gonzalez-Huarriz M, Bitarte N, Rodriguez J, Zarate R, Bandres E, Garcia-Foncillas J: Identification of predictive circulating biomarkers of bevacizumab-containing regimen efficacy in pre-treated metastatic colorectal cancer patients. Br J Cancer 2012, 107(2):287-290.
57. Simkens LH, Tol J, Terstappen LW, Teerenstra S, Punt CJ, Nagtegaal ID: The predictive and prognostic value of circulating endothelial cells in advanced colorectal cancer patients receiving first-line chemotherapy and bevacizumab. Ann Oncol 2010, 21(12):2447-2448.
58. Ronzoni M, Manzoni M, Mariucci S, Loupakis F, Brugnatelli S, Bencardino K, Rovati B, Tinelli C, Falcone A, Villa E, Danova M: Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients. Ann Oncol 2010, 21(12):2382-2389.
59. Matsusaka S, Suenaga M, Mishima Y, Takagi K, Terui Y, Mizunuma N, Hatake K: Circulating endothelial cells predict for response to bevacizumabbased chemotherapy in metastatic colorectal cancer. Cancer Chemother Pharmacol 2011, 68(3):763-768.
60. Matsusaka S, Mishima Y, Suenaga M, Terui Y, Kuniyoshi R, Mizunuma N, Hatake K: Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab. Cancer 2011, 117(17):4026-4032.
61. Malka D, Boige V, Jacques N, Vimond N, Adenis A, Boucher E, Pierga JY, Conroy T, Chauffert B, François E, Guichard P, Galais MP, Cvitkovic F, Ducreux M, Farace F: Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol 2012, 23(4):919-927.
62. Lieb W, Safa R, Benjamin EJ, Xanthakis V, Yin X, Sullivan LM, Larson MG, Smith HM, Vita JA, Mitchell GF, Sawyer DB, Vasan RS: Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function. Eur Heart J 2009, 30:1121-1127.
63. Koutras AK, Antonacopoulou AG, Eleftheraki AG, Dimitrakopoulos FI, Koumarianou A, Varthalitis I, Fostira F, Sgouros J, Briasoulis E, Bournakis E, Bafaloukos D, Bompolaki I, Galani E, Kalogeras KT, Pectasides D, Fountzilas G, Kalofonos HP: Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecanbased chemotherapy and bevacizumab. Pharmacogenomics J. in press.
64. Lambrechts D, Claes B, Delmar P, Reumers J, Mazzone M, Yesilyurt BT, Devlieger R, Verslype C, Tejpar S, Wildiers H, de Haas S, Carmeliet P, Scherer SJ, Van Cutsem E: VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol 2012, 13(7):724-733.
65. Davies RL, Grosse VA, Kucherlapati R, Bothwell M: Genetic analysis of epidermal growth factor action: assignment of human epidermal growth factor receptor gene to chromosome 7. Proc Natl Acad Sci USA 1980, 77(7):4188-4192.
66. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007, 356(2):125-134.
67. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007, 356(2):115-124.
68. Ebi H, Corcoran RB, Singh A, Chen Z, Song Y, Lifshits E, Ryan DP, Meyerhardt JA, Benes C, Settleman J, Wong KK, Cantley LC, Engelman JA: Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J Clin Invest 2011, 121(11):4311-4321.
69. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004, 22(7):1201-1208.
70. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004, 351(4):337-345.
71. Vincenzi B, Santini D, Rabitti C, Coppola R, Beomonte Zobel B, Trodella L, Tonini G: Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single-centre phase II trial. Br J Cancer 2006, 94(6):792-797.
72. Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK: Multicentre phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irintecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 2006, 24:4914-4921.
73. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ: Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007, 357(20):2040-2048.
74. Gibson TB, Ranganathan A, Grothey A: Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin Colorectal Cancer 2006, 6(1):29-31.
75. Wainberg Z, Hecht JR: A phase III randomized, open-label, controlled trial of chemotherapy and bevacizumab with or without panitumumab in the first-line treatment of patients with metastatic colorectal cancer. Clin Colorectal Cancer 2006, 5(5):363-367.
76. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG: 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 2007, 25(13):1658-1664.
77. Siena S, Peeters M, Van Cutsem E, Humblet Y, Conte P, Bajetta E, Comandini D, Bodoky G, Van Hazel G, Salek T, Wolf M, Devercelli G, Woolley M, Amado RG: Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab. Br J Cancer 2007, 97(11):1469-1474.
78. Li T, Perez-Soler R: Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol 2009, 4(2):107-119.
79. Mitchell EP, Piperdi B, Lacouture ME, Shearer H, Iannotti N, Pillai MV, Xu F, Yassine M: The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status. Clin Colorectal Cancer 2011, 10(4):333-339.
80. Pinto C, Barone CA, Girolomoni G, Russi EG, Merlano MC, Ferrari D, Maiello E, American Society of Clinical Oncology, European Society of Medical Oncology: Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy. Oncologist 2011, 16(2):228-238.
81. George TJ Jr, Laplant KD, Walden EO, Davis AB, Riggs CE, Close JL, George SN, Lynch JW: Managing cetuximab hypersensitivity-infusion reactions: incidence, risk factors, prevention, and retreatment. J Support Oncol 2010, 8(2):72-77.
82. Berlin J, Van Cutsem E, Peeters M, Hecht JR, Ruiz R, Wolf M, Amado RG, Meropol NJ: Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): a pooled analysis of five clinical trials [abstract]. J Clin Oncol 2007, 25(18S):4134.
83. Stintzing S, Kapaun C, Laubender RP, Jung A, Neumann J, Modest DP, Giessen C, Moosmann N, Wollenberg A, Kirchner T, Heinemann V: Prognostic value of cetuximab related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with parameters of the EGFR signal transduction pathway. Results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer 2013, 132(1):236-245.
84. Saif MW, Kaley K, Chu E, Copur MS: Safety and efficacy of panitumumab therapy after progression with cetuximab: experience at two institutions. Clin Colorectal Cancer 2010, 9(5):315-318.
85. Peeters M, Siena S, Van Cutsem E, Sobrero A, Hendlisz A, Cascinu S, Kalofonos H, Devercelli G, Wolf M, Amado RG: Association of progressionfree survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer 2009, 115(7):1544-1554.
86. Lacouture ME, Mitchell EP, Shearer H, Iannotti N, Piperdi B, Pillai MV, Xu F, Yassine M: Impact of pre-emptive skin toxicity treatment on panitumumabrelated skin toxicities quality of life in patients with metastatic colorectal cancer: Results from STEPP. In ASCO Gastrointestinal Cancers Symposium: 15-17 January. San Francisco, CA. Alexandria: ASCO; 2009.
87. Graziano F, Ruzzo A, Loupakis F, Canestrari E, Santini D, Catalano V, Bisonni R, Torresi U, Floriani I, Schiavon G, Andreoni F, Maltese P, Rulli E, Humar B, Falcone A, Giustini L, Tonini G, Fontana A, Masi G, Magnani M: Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J Clin Oncol 2008, 26(9):1427-1434.
88. Garm Spindler KL, Pallisgaard N, Rasmussen AA, Lindebjerg J, Andersen RF, Crüger D, Jakobsen A: The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer. Ann Oncol 2009, 20(5):879-884.
89. Mok T, Wu YL, Zhang L: A small step towards personalized medicine for non-small cell lung cancer. Discov Med 2009, 8(43):227-231.
90. Pander J, Gelderblom H, Antonini NF, Tol J, van Krieken JH, van der Straaten T, Punt CJ, Guchelaar HJ: Correlation of FCGR3A and EGFR germline polymorphisms with the efficacy of cetuximab in KRAS wild-type metastatic colorectal cancer. Eur J Cancer 2010, 46(10):1829-1834.
91. Dahan L, Norguet E, Etienne-Grimaldi MC, Formento JL, Gasmi M, Nanni I, Gaudart J, Garcia S, Ouafik L, Seitz JF, Milano G: Pharmacogenetic profiling and cetuximab outcome in patients with advanced colorectal cancer. BMC Cancer 2011, 11:496.
92. Grossman AH, Samowitz WS: Epidermal growth factor receptor pathway mutations and colorectal cancer therapy. Arch Pathol Lab Med 2011, 135:1278-1282.
93. Ålgars A, Lintunen M, Carpén O, Ristamäki R, Sundström J: EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer. Br J Cancer 2011, 105(2):255-262.
94. Ensinger C, Sterlacci W: Implications of EGFR PharmDx kit for cetuximab eligibility. Expert Rev Mol Diagn 2008, 8(2):141-148.
95. Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB: Cetuximab shows activity in CRC patients with tumours that do not express the EGFR by immunohistochemistry. J Clin Oncol 2005, 23:1803-1810.
96. Kang MJ, Hong YS, Kim KP, Kim SY, Baek JY, Ryu MH, Lee JL, Chang HM, Kim MJ, Chang HJ, Kang YK, Kim TW: Biweekly cetuximab plus irinotecan as second-line chemotherapy for patients with irinotecan-refractory and KRAS wild-type metastatic colorectal cancer according to epidermal growth factor receptor expression status. Invest New Drugs 2011, 30(4):1607-1613.
97. Fearon ER: Molecular genetics of colorectal cancer. Annu Rev Pathol 2011, 6:479-507.
98. Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA: Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 2009, 101(3):465-472.
99. Andreyev HJ, Tilsed JV, Cunningham D, Sampson SA, Norman AR, Schneider HJ, Clarke PA: K-ras mutations in patients with early colorectal cancers. Gut 1997, 41(3):323-329.
100. Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA: Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst 1998, 90(9):675-684.
101. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O'Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, et al: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer 2011, 85(5):692-696.
102. Edkins S, O'Meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H, Dalgliesh G, Forbes S, Hunter C, Smith R, Stephens P, Goldstraw P, Nicholson A, Chan TL, Velculescu VE, Yuen ST, Leung SY, Stratton MR, Futreal PA: Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther 2006, 5(8):928-932.
103. Janakiraman M, Vakiani E, Zeng Z, Pratilas CA, Taylor BS, Chitale D, Halilovic E, Wilson M, Huberman K, Ricarte Filho JC, Persaud Y, Levine DA, Fagin JA, Jhanwar SC, Mariadason JM, Lash A, Ladanyi M, Saltz LB, Heguy A, Paty PB, Solit DB: Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res 2010, 70(14):5901-5911.
104. Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Côté JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P: KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006, 66(8):3992-3995.
105. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008, 26(10):1626-1634.
106. Lin JS, Webber EM, Senger CA, Holmes RS, Whitlock EP: Systematic review of pharmacogenetic testing for predicting clinical benefit to anti-EGFR therapy in met CRC. Am J Cancer Res 2011, 1(5):650-662.
107. Loupakis F, Cremolini C, Salvatore L, Schirripa M, Lonardi S, Vaccaro V, Cuppone F, Giannarelli D, Zagonel V, Cognetti F, Tortora G, Falcone A, Bria E: Clinical impact of anti-epidermal growth factor receptor monoclonal antibodies in first-line treatment of metastatic colorectal cancer: metaanalytical estimation and implications for therapeutic strategies. Cancer 2012, 118(6):1523-1532.
108. Vale CL, Tierney JF, Fisher D, Adams RA, Kaplan R, Maughan TS, Parmar MK, Meade AM: Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis. Cancer Treat Rev 2012, 38(6):618-625.
109. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL: American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009, 27(12):2091-2096.
110. Cripps C, Gill S, Ahmed S, Colwell B, Dowden S, Kennecke H, Maroun J, Samson B, Thirlwell M, Wong R: Consensus recommendations for the use of anti-EGFR therapies in metastatic colorectal cancer. Curr Oncol 2010, 17(6):39-45.
111. Aubin F, Gill S, Burkes R, Colwell B, Kamel-Reid S, Koski S, Pollett A, Samson B, Tehfe M, Wong R, Young S, Soulières D: Canadian Expert Group consensus recommendations: KRAS testing in colorectal cancer. Curr Oncol 2011, 8(4):e180-e184.
112. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, et al: 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 2010, 11(8):753-762.
113. Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE: Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 2010, 16(3):790-799.
114. Mariani P, Lae M, Degeorges A, Cacheux W, Lappartient E, Margogne A, Pierga JY, Girre V, Mignot L, Falcou MC, Salmon RJ, Delattre O, De Cremoux P: Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis. Anticancer Res 2010, 30(10):4229-4235.
115. Bösmüller H, Kranewitter W, Webersinke G, Rumpold H, Hackl M, Fend F: Morphological and molecular heterogeneity in colorectal neoplasms with K-RAS mutation. A report of two cases. Pathol Res Pract 2011, 207(6):399-402.
116. Farber L, Efrati E, Elkin H, Peerless Y, Sabo E, Ben-Izhak O, Hershkovitz D: Molecular morphometric analysis shows relative intra-tumoural homogeneity for KRAS mutations in colorectal cancer. Virchows Arch 2011, 459(5):487-493.
117. Oltedal S, Aasprong OG, Møller JH, Kørner H, Gilje B, Tjensvoll K, Birkemeyer EM, Heikkilä R, Smaaland R, Nordgård O: Heterogeneous distribution of Kras mutations in primary colon carcinomas: implications for EGFRdirected therapy. Int J Colorectal Dis 2011, 26(10):1271-1277.
118. Franklin WA, Haney J, Sugita M, Bemis L, Jimeno A, Messersmith WA: KRAS mutation: comparison of testing methods and tissue sampling techniques in colon cancer. J Mol Diagn 2010, 12(1):43-50.
119. Richman SD, Chambers P, Seymour MT, Daly C, Grant S, Hemmings G, Quirke P: Intra-tumoral heterogeneity of KRAS and BRAF mutation status in patients with advanced colorectal cancer (aCRC) and cost effectiveness of multiple sample testing. Anal Cell Pathol (Amst) 2011, 34(1-2):61-66.
120. Blank PR, Moch H, Szucs TD, Schwenkglenks M: KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a Swiss perspective. Clin Cancer Res 2011, 17(19):6338-6346.
121. Vijayaraghavan A, Efrusy MB, Göke B, Kirchner T, Santas CC, Goldberg RM: Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany. Int J Cancer 2012, 131(2):438-445.
122. French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, Shepherd L, Windschitl HE, Thibodeau SN: Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res 2008, 14(11):3408-3415.
123. Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, Rougier P, Lievre A, Landi B, Boige V, Ducreux M, Ychou M, Bibeau F, Bouché O, Reid J, Stone S, Penault-Llorca F: Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 2009, 27(35):5924-5930.
124. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A: Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008, 26(35):5705-5712.
125. Mao C, Liao RY, Qiu LX, Wang XW, Ding H, Chen Q: BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol Biol Rep 2011, 38(4):2219-2223.
126. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R: Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 2012, 483(7387):100-103.
127. Zhao L, Vogt PK: Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci USA 2008, 105(7):2652-2657.
128. Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, McBryan T, Doyle B, McKay C, Oien KA, Enders GH, Zhang R, Sansom OJ, Adams PD: Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell 2011, 42(1):36-49.
129. Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A: PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 2009, 69(5):1851-1857.
130. Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, Lambrechts D, Van Cutsem E, Tejpar S: PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 2009, 15(9):3184-3188.
131. Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR: Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res 2004, 64(9):3014-3021.
132. Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M, Molinari F, De Dosso S, Saletti P, Martini M, Cipani T, Marrapese G, Mazzucchelli L, Lamba S, Veronese S, Frattini M, Bardelli A, Siena S: Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS One. 2009, 4(10):e7287.
133. Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, Frattini M, Riva C, Andreola S, Bajetta E, Bertario L, Leo E, Pierotti MA, Pilotti S: PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 2009, 20(1):84-90.
134. Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, Rajdev L, Mariadason JM, Tanaka K, Goel S: PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to antiepidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 2012, 11(2):143-150.
135. Ulivi P, Capelli L, Valgiusti M, Zoli W, Scarpi E, Chiadini E, Rosetti P, Bravaccini S, Calistri D, Saragoni L, Casadei Gardini A, Ragazzini A, Frassineti GL, Amadori D, Passardi A: Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study. J Transl Med 2012, 10(1):87.
136. Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, Camponovo A, Etienne LL, Cavalli F, Mazzucchelli L: PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007, 97(8):1139-1145.
137. Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Börger ME, van Cleef PH, van Krieken JH, Punt CJ, Nagtegaal ID: Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 2010, 46(11):1997-2009.
138. Loupakis F, Pollina L, Stasi I, Ruzzo A, Scartozzi M, Santini D, Masi G, Graziano F, Cremolini C, Rulli E, Canestrari E, Funel N, Schiavon G, Petrini I, Magnani M, Tonini G, Campani D, Floriani I, Cascinu S, Falcone A: PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009, 27(16):2622-2629.
139. Negri FV, Bozzetti C, Lagrasta CA, Crafa P, Bonasoni MP, Camisa R, Pedrazzi G, Ardizzoni A: PTEN status in advanced colorectal cancer treated with cetuximab. Br J Cancer 2010, 102(1):162-164.
140. Barbier A, Domont J, Magné N, Goldmard JL, Genestie C, Hannoun C, Vaillant JC, Bellanger A, Khayat D, Capron F, Spano JP: Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab. Bull Cancer 2010, 97(2):E9-E15.
141. Perkins G, Lièvre A, Ramacci C, Méatchi T, de Reynies A, Emile JF, Boige V, Tomasic G, Bachet JB, Bibeau F, Bouché O, Penault-Llorca F, Merlin JL, Laurent-Puig P: Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti-EGFR antibodies in colorectal cancer. Int J Cancer 2010, 127(6):1321-1331.
142. FDA: Draft guidance for Industry and Food and Drug Administration Staff-in vitro companion diagnostic devices. [http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm262292.htm]
143. Rinaldi F, George E, Adler AI: NICE guidance on cetuximab, bevacizumab, and panitumumab for treatment of metastatic colorectal cancer after first-line chemotherapy. Lancet Oncol 2012, 13(3):233-234.
144. Characiejus D, Hodzic J, Jacobs JJL: "First do no harm" and the importance of prediction in oncology. EPMA J 2010, 1(3):369-375.
145. Clausson CM, Grundberg I, Weibrecht I, Nilsson M, Söderberg O: Methods for analysis of the cancer microenvironment and their potential for disease prediction, monitoring and personalized treatments. EPMA J 2012, 3:7.
146. Ibrahim AEK, Arends MJ: Molecular typing of colorectal cancer: applications in diagnosis and treatment. Diagnostic Histopathology 2012, 18(2):70-80.