The role of personalized medicine in metastatic colorectal cancer: An evolving landscape

Therapeutic Advances in Gastroenterology

Volumn 6, Issue 5, 2013, Pages 381-395

  Moorcraft, Sing Y ^a   Smyth, Elizabeth C ^a   Cunningham, David ^a  

^a ROYAL MARSDEN HOSPITAL   (United Kingdom)

Author keywords

biomarker; colorectal cancer; personalized medicine; targeted therapy

Indexed keywords

ACETYLSALICYLIC ACID; AMPHIREGULIN; BEVACIZUMAB; CAPECITABINE; CETUXIMAB; DALOTUZUMAB; EPIREGULIN; ERLOTINIB; FLUOROURACIL; GEFITINIB; IPILIMUMAB; IRINOTECAN; METHOTREXATE; MITOGEN ACTIVATED PROTEIN KINASE; OXALIPLATIN; PANITUMUMAB; PERIFOSINE; REGORAFENIB; SELUMETINIB; SOMATOMEDIN; TRASTUZUMAB; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN ANTIBODY; VEMURAFENIB;

ADENOMA; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; CANCER COMBINATION CHEMOTHERAPY; CANCER GENETICS; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CHROMOSOMAL INSTABILITY; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); COLON POLYPOSIS; CPG ISLAND; DISEASE COURSE; DRUG BINDING; DRUG EFFICACY; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE MUTATION; HEREDITARY NONPOLYPOSIS COLORECTAL CANCER; HUMAN; IMMUNOTHERAPY; MELANOMA; METASTATIC COLORECTAL CANCER; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; MOLECULAR BIOLOGY; MONOTHERAPY; OVERALL SURVIVAL; PERSONALIZED MEDICINE; PHENOTYPE; PRIORITY JOURNAL; REVIEW; TUMOR SUPPRESSOR GENE;

EID: 84883430683     PISSN: 1756283X     EISSN: 17562648     Source Type: Journal    
DOI: 10.1177/1756283X13491797     Document Type: Article

References (133)

1. Adams R. Fisher D. Farragher S. Scott A. Smith C. James M. et al (2012) Epiregulin (EREG) and amphiregulin (AREG) gene expression to predict response to cetuximab therapy in combination with oxaliplatin (Ox) and 5FU in first-line treatment of advanced colorectal cancer (aCRC). J Clin Oncol 30(Suppl.): abstract 3516.
2. Alymani N. Smith M. Williams D. Petty R. (2010) Predictive biomarkers for personalised anti-cancer drug use: discovery to clinical implementation. Eur J Cancer 46: 869-879.
3. Amado R. Wolf M. Peeters M. van Cutsem E. Siena S. Freeman D. et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26: 1626-1634.
4. Baker J. Dutta D. Watson D. Maddala T. Munneke B. Shak S. et al (2011) Tumour gene expression predicts response to cetuximab in patients with KRAS wild-type metastatic colorectal cancer. Br J Cancer 104: 488-495.
5. Baldus S. Schaefer K. Engers R. Hartleb D. Stoecklein N. Gabbert H. (2010) Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 16: 790-799.
6. Barbara C. Martin V. Molinari F. Landi L. Riva A. Saletti P. et al (2012) Use of HER 2 gene amplification to identify patients with metastatic colorectal cancer resistant to anti-EGFR monoclonal antibodies. J Clin Oncol 30(Suppl. 4): abstract 474.
7. Barber T. Vogelstein B. Kinzler K. Velculescu V. (2004) Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med 351: 2883.
8. Bardelli A. Siena S. (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28: 1254-1261.
9. Bendell J. Ervin T. Senzer N. Richards D. Firdaus I. Lockhart A. et al (2012) Results of the X-PECT study: a phase III randomized double-blind, placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC). J Clin Oncol 30(Suppl.): abstract LBA3501.
10. Bertotti A. Migliardi G. Galimi F. Sassi F. Torti D. Isella C. et al (2011) A molecularly annotated platform of patient-derived xenografts (‘xenopatients’) identifies HER 2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 1: 508-523.
11. Blanke C. Goldberg R. Grothey A. Mooney M. Roach N. Saltz L. et al (2011) KRAS and colorectal cancer: ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice. Oncologist 16: 1061-1068.
12. Bokemeyer C. Bondarenko I. Makhson A. Hartmann J. Aparicio J. de Braud F. et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27: 663-671.
13. Bokemeyer C. van Cutsem E. Rougier P. Ciardiello F. Heeger S. Schlichting M. et al (2012) Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 48: 1466-1475.
14. Borner M. Koeberle D. Von Moos R. Saletti P. Rauch D. Hess V. et al (2008) Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol 19: 1288-1292.
15. Boulay J. Mild G. Lowy A. Reuter J. Lagrange M. Terracciano L. et al (2002) SMAD 4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer. Br J Cancer 87: 630–634.
16. Brahmer J. Tykodi S. Chow L. Hwu W. Topalian S. Hwu P. et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366: 2455-2465.
17. Braun M. Richman S. Quirke P. Daly C. Adlard J. Elliott F. et al (2008) Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol 26: 2690-2698.
18. Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330-337.
19. Chapman P. Hauschild A. Robert C. Haanen J. Ascierto P. Larkin J. et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364: 2507-2516.
20. Chung K. Shia J. Kemeny N. Shah M. Schwartz G. Tse A. et al (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23: 1803-1810.
21. Clark J. Niedzwiecki D. Hollis D. Mayer R. (2003) Phase II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. Proc Am Soc Clin Oncol 22: abstract 3584.
22. Cunningham D. Atkin W. Lenz H. Lynch H. Minsky B. Nordlinger B. et al (2010) Colorectal cancer. Lancet 375: 1030-1047.
23. Cunningham D. Humblet Y. Siena S. Khayat D. Bleiberg H. Santoro A. et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351: 337-345.
24. de Roock W. Claes B. Bernasconi D. de Schutter J. Biesmans B. Fountzilas G. et al (2010) 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: 753-762.
25. Deschoolmeester V. Baay M. Specenier P. Lardon F. Vermorken J. (2010) A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist 15: 699-731.
26. Dewdney A. Cunningham D. Barbachano Y. Chau I. (2012) 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 liver-only metastases unsuitable for upfront resection. Br J Cancer 106: 1718-1721.
27. Diamandis M. White N. Yousef G. (2010) Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res 8: 1175-1187.
28. Dienstmann R. Serpico D. Rodon J. Saura C. Macarulla T. Elez E. et al (2012) Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. Mol Cancer Ther 11: 2062-2071.
29. Di Nicolantonio F. Arena S. Tabernero J. Grosso S. Molinari F. Macarulla T. et al (2010) Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest 120: 2858-2866.
30. Di Nicolantonio F. Martini M. Molinari F. Sartore-Bianchi A. Arena S. Saletti P. et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26: 5705-5712.
31. Douillard J. Siena S. Cassidy J. Tabernero J. Burkes R. Barugel M. et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX 4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28: 4697-4705.
32. Fallik D. Borrini F. Boige V. Viguier J. Jacob S. Miquel C. et al (2003) Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 63: 5738-5744.
33. Ferte C. Andre F. Soria J. (2010) Molecular circuits of solid tumors: prognostic and predictive tools for bedside use. Nat Rev Clin Oncol 7: 367-380.
34. Finocchiaro G. Cappuzzo F. Jänne P. Bencardino K. Carnaghi C. Franklin W. et al (2007) EGFR, HER 2 and Kras as predictive factors for cetuximab sensitivity in colorectal cancer. J Clin Oncol 25: 4021.
35. Folprecht G. Gruenberger T. Bechstein W. Raab H. Lordick F. Hartmann J. et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11: 38-47.
36. Frank M. Mittendorf T. (2013) Influence of pharmacogenomic profiling prior to pharmaceutical treatment in metastatic colorectal cancer on cost effectiveness: a systematic review. Pharmaco Economics 31: 215-228.
37. Garcia-Carbonero R. Rivera F. Maurel J. Ayoub J. Moore M. Cervantes-Ruiperez A. et al (2012) A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC): CP12-0709/NCT00862784. J Clin Oncol 30(Suppl. 4): abstract 533.
38. Gerlinger M. Rowan A. Horswell S. Larkin J. Endesfelder D. Gronroos E. et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883-892.
39. Gervaz P. Bucher P. Morel P. (2004) Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol 88: 261-266.
40. Giantonio B. Catalano P. Meropol N. O'Dwyer P. Mitchell E. Alberts S. et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25: 1539-1544.
41. Grady W. Care thers J. (2008) Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 135: 1079-1099.
42. Greystoke A. Mullamitha S. (2012) How many diseases are colorectal cancer? Gastroenterol Res Pract 2012: 564741.
43. Grothey A. Sugrue M. Purdie D. Dong W. Sargent D. Hedrick E. et al (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26: 5326-5334.
44. Grothey A. van Cutsem E. Sobrero A. Siena S. Falcone A. Ychou M. et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 303-312.
45. Gruenberger B. Tamandl D. Schueller J. Scheithauer W. Zielinski C. Herbst F. et al (2008) Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26: 1830-1835.
46. Hecht J. Mitchell E. Chidiac T. Scroggin C. Hagenstad C. Spigel D. et al (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27: 672-680.
47. Hewish M. Lord C. Martin S. Cunningham D. Ashworth A. (2010) Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol 7: 197-208.
48. Higgins B. Kolinsky K. Schostack K. Bollag G. Lee R. Su F. et al (2012) Efficacy of vemurafenib (V), a selective V600EBRAF inhibitor, as monotherapy or in combination with erlotinib (Erl) or erbitux (Erb) and irinotecan (Iri) doublets and triplets in a colorectal cancer (CRC) xenograft model. J Clin Oncol 30(Suppl. 4): abstract 494.
49. Hochster H. Messersmith W. O'Neil B. Groshen S. Cohen D. Denlinger C. et al (2012) Second-line therapy of KRAS-mutated (KRASm) metastatic colorectal cancer (CRC) with the MEK inhibitor selumetinib ([SEL], AZ6244, ARRY-142886) in combination with irinotecan (IRI): An AGICC study. J Clin Oncol 30(Suppl. 34): abstract 380.
50. Hu Y. Patil S. Panasiewicz M. Li W. Hauser J. Humphrey L. et al (2008) Heterogeneity of receptor function in colon carcinoma cells determined by cross-talk between type I insulin-like growth factor receptor and epidermal growth factor receptor. Cancer Res 68: 8004-8013.
51. Hurwitz H. Fehrenbacher L. Novotny W. Cartwright T. Hainsworth J. Heim W. et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342.
52. Ihle N. Lemos R. Jr Wipf P. Yacoub A. Mitchell C. Siwak D. et al (2009) Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer Res 69: 143-150.
53. International Agency for Research on Cancer (2010) GLOBOCAN 2008 v2.0, Estimated cancer incidence, mortality prevalence and disability-adjusted life years (DALYs) worldwide in 2008. Available at: http://globocan.iarc.fr (accessed 14 May 2013).
54. Jacobs B. de Roock W. Piessevaux H. van Oirbeek R. Biesmans B. de Schutter J. et al (2009) Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 27: 5068-5074.
55. Jang K. Song Y. Jang S. Min K. Na W. Jang S. et al (2010) Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma. Histopathology 56: 229-239.
56. Jenkins M. Hayashi S. O'Shea A. Burgart L. Smyrk T. Shimizu D. et al (2007) Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology 133: 48-56.
57. Jonker D. O'Callaghan C. Karapetis C. Zalcberg J. Tu D. Au H. et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357: 2040-2048.
58. Kabbinavar F. Schulz J. McCleod M. Patel T. Hamm J. Hecht J. et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23: 3697-3705.
59. Karapetis C. Khambata-Ford S. Jonker D. O'Callaghan C. Tu D. Tebbutt N. et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359: 1757-1765.
60. Kavanagh D. Chambers G. O'Grady L. Barry K. Waldron R. Bennani F. et al (2009) Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer 9: 1.
61. Kelley R. Venook A. (2011) Prognostic and predictive markers in stage II colon cancer: is there a role for gene expression profiling? Clin Colorectal Cancer 10: 73-80.
62. Kerber R. Neklason D. Samowitz W. Burt R. (2005) Frequency of familial colon cancer and hereditary nonpolyposis colorectal cancer (Lynch syndrome) in a large population database. Fam Cancer 4: 239-244.
63. Koopman M. Venderbosch S. Nagtegaal I. van Krieken J. Punt C. (2009 a) A review on the use of molecular markers of cytotoxic therapy for colorectal cancer, what have we learned? Eur J Cancer 45: 1935-1949.
64. Koopman M. Venderbosch S. van Tinteren H. Ligtenberg M. Nagtegaal I. van Krieken J. et al (2009 b) Predictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomised CAIRO study. Eur J Cancer 45: 1999-2006.
65. Kopetz S. Desai J. Chan E. Hecht J. O'Dwyer P. Lee R. et al (2010) PLX 4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J Clin Oncol 15S: 3534.
66. Koutras A. Antonacopoulou A. Eleftheraki A. Dimitrakopoulos F. Koumarianou A. Varthalitis I. et al (2012) Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. Pharmacogenomics J 12: 468-475.
67. Kurzrock R. Tsimberidou A. Hong D. Wheler J. Falchook G. Fu S. et al (2012) Pursuing molecular stratification in phase I trials. European Journal of Cancer 48(Suppl. 6): 9.
68. Laurent-Puig P. Cayre A. Manceau G. Buc E. Bachet J. Lecomte T. et al (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27: 5924-5930.
69. Lee A. Swanton C. (2012) Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics. Biochem Pharmacol 83: 1013-1020.
70. Liao X. Lochhead P. Nishihara R. Morikawa T. Kuchiba A. Yamauchi M. et al (2012) Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 367: 1596-1606.
71. Liu L. Li Y. Li S. Hu N. He Y. Pong R. et al (2012) Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012: 251364.
72. Loupakis F. Pollina L. Stasi I. Ruzzo A. Scartozzi M. Santini D. et al (2009 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 27: 2622-2629.
73. Loupakis F. Ruzzo A. Cremolini C. Vincenzi B. Salvatore L. Santini D. et al (2009 b) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101: 715-721.
74. Mao M. Tian F. Mariadason J. Tsao L. Lemos R. Jr Dayyani F. et al (2012) Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res 19: 657-667.
75. Markowitz S. Bertagnolli M. (2009) Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 361: 2449-2460.
76. Martin S. McCarthy A. Barber L. Burgess D. Parry S. Lord C. et al (2009) Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol Med 1: 323-337.
77. Maughan T. Adams R. Smith C. Meade A. Seymour M. Wilson R. et al (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377: 2103-2114.
78. Morabito A. Piccirillo M. Costanzo R. Sandomenico C. Carillio G. Daniele G. et al (2010) Vandetanib: an overview of its clinical development in NSCLC and other tumors. Drugs Today (Barc) 46: 683-698.
79. Moroni M. Veronese S. Benvenuti S. Marrapese G. Sartore-Bianchi A. Di Nicolantonio F. et al (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6: 279-286.
80. O'Mahony D. Morris J. Quinn C. Gao W. Wilson W. Gause B. et al (2007) A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin Cancer Res 13: 958-964.
81. Oltedal S. Aasprong O. Moller J. Korner H. Gilje B. Tjensvoll K. et al (2011) Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy. Int J Colorectal Dis 26: 1271-1277.
82. Palomaki G. Bradley L. Douglas M. Kolor K. Dotson W. (2009) Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med 11: 21-34.
83. Pectasides D. Papaxoinis G. Kalogeras K. Eleftheraki A. Xanthakis I. Makatsoris T. et al (2012) XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis. BMC Cancer 12: 271.
84. Peeters M. Douillard J. van Cutsem E. Siena S. Zhang K. Williams R. et al (2013) Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol 31: 759-765.
85. Peeters M. Price T. Cervantes A. Sobrero A. Ducreux M. Hotko Y. et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28: 4706-4713.
86. Pohl M. Stricker I. Schoeneck A. Schulmann K. Klein-Scory S. Schwarte-Waldhoff I. et al (2009) Antitumor activity of the HER 2 dimerization inhibitor pertuzumab on human colon cancer cells in vitro and in vivo. J Cancer Res Clin Oncol 135: 1377-1386.
87. Prahallad A. Sun C. Huang S. Di Nicolantonio F. Salazar R. Zecchin D. et al (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483: 100-103.
88. Ramanathan R. Hwang J. Zamboni W. Sinicrope F. Safran H. Wong M. et al (2004) Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trial. Cancer Invest 22: 858-865.
89. Razis E. Briasoulis E. Vrettou E. Skarlos D. Papamichael D. Kostopoulos I. et al (2008) Potential value of PTEN in predicting cetuximab response in colorectal cancer: an exploratory study. BMC Cancer 8: 234.
90. Ribic C. Sargent D. Moore M. Thibodeau S. French A. Goldberg R. et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349: 247-257.
91. Richman S. Seymour M. Chambers P. Elliott F. Daly C. Meade A. et al (2009) KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol 27: 5931-5937.
92. Saltz L. Clarke S. Diaz-Rubio E. Scheithauer W. Figer A. Wong R. et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26: 2013-2019.
93. Saltz L. Meropol N. Loehrer P. Sr. Needle M. Kopit J. Mayer R. (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22: 1201-1208.
94. Samowitz W. Albertsen H. Herrick J. Levin T. Sweeney C. Murtaugh M. et al (2005) Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology 129: 837-845.
95. Santoro A. Comandone A. Rimassa L. Granetti C. Lorusso V. Oliva C. et al (2008) A phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer. Ann Oncol 19: 1888-1893.
96. Sargent D. Marsoni S. Monges G. Thibodeau S. Labianca R. Hamilton S. et al (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28: 3219-3226.
97. Sartore-Bianchi A. Di Nicolantonio F. Nichelatti M. Molinari F. de Dosso S. Saletti P. et al (2009 a) Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PloS ONE 4: e7287.
98. Sartore-Bianchi A. Martini M. Molinari F. Veronese S. Nichelatti M. Artale S. et al (2009 b) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69: 1851-1857.
99. Sawai H. Yasuda A. Ochi N. Ma J. Matsuo Y. Wakasugi T. et al (2008) Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival. BMC Gastroenterol 8: 56.
100. Scartozzi M. Galizia E. Chiorrini S. Giampieri R. Berardi R. Pierantoni C. et al (2009) Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol 20: 227-230.
101. Scartozzi M. Mandolesi A. Giampieri R. Pierantoni C. Loupakis F. Zaniboni A. et al (2010) Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan. Int J Cancer 127: 1941-1947.
102. Schmoll H. Cunningham D. Sobrero A. Karapetis C. Rougier P. Koski S. et al (2012) Cediranib with mFOLFOX 6 versus bevacizumab with mFOLFOX 6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 30: 3588-3595.
103. Sclafani F. Gullo G. Sheahan K. Crown J. (2012) BRAF mutations in melanoma and colorectal cancer: A single oncogenic mutation with different tumour phenotypes and clinical implications. Crit Rev Oncol Hematol 11 December (Epub ahead of print).
104. Shirota Y. Stoehlmacher J. Brabender J. Xiong Y. Uetake H. Danenberg K. et al (2001) ERCC 1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 19: 4298-4304.
105. Siena S. Sartore-Bianchi A. Di Nicolantonio F. Balfour J. Bardelli A. (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101: 1308-1324.
106. Sinicrope F. Sargent D. (2012) Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res 18: 1506-1512.
107. Sobrero A. Maurel J. Fehrenbacher L. Scheithauer W. Abubakr Y. Lutz M. et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26: 2311-2319.
108. Souglakos J. Kalykaki A. Vamvakas L. Androulakis N. Kalbakis K. Agelaki S. et al (2007) Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy. Ann Oncol 18: 305-310.
109. Spindler K. Pallisgaard N. Lindebjerg J. Frifeldt S. Jakobsen A. (2011) EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer. BMC Cancer 11: 107.
110. Stoehlmacher J. Park D. Zhang W. Yang D. Groshen S. Zahedy S. et al (2004) A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91: 344-354.
111. Sun X. Ahmadi A. Arbman G. Wallin A. Asklid D. Zhang H. (2005) Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P 1 genes in relation to colorectal cancer risk and patients’ survival. World J Gastroenterol 11: 6875-6879.
112. Tejpar S. Celik I. Schlichting M. Sartorius U. Bokemeyer C. van Cutsem E. (2012) Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol 30: 3570-3577.
113. Tol J. Dijkstra J. Klomp M. Teerenstra S. Dommerholt M. Vink-Borger M. et al (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46: 1997-2009.
114. Tol J. Koopman M. Cats A. Rodenburg C. Creemers G. Schrama J. et al (2009 a) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360: 563-572.
115. Tol J. Nagtegaal I. Punt C. (2009 b) BRAF mutation in metastatic colorectal cancer. N Engl J Med 361: 98-99.
116. Topalian S. Hodi F. Brahmer J. Gettinger S. Smith D. McDermott D. et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366: 2443-2454.
117. Tournigand C. Samson B. Scheithauer W. Lledo G. Viret F. Andre T. et al (2012) Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): efficacy and safety results of the International GERCOR DREAM phase III trial.J Clin Oncol 30(Suppl.): abstract LBA3500.
118. Townsley C. Major P. Siu L. Dancey J. Chen E. Pond G. et al (2006) Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Br J Cancer 94: 1136-1143.
119. Troiani T. Zappavigna S. Martinelli E. Addeo S. Stiuso P. Ciardiello F. et al (2013) Optimizing treatment of metastatic colorectal cancer patients with anti-EGFR antibodies: overcoming the mechanisms of cancer cell resistance. Expert Opin Biol Ther 13: 241-255.
120. Tveit K. Guren T. Glimelius B. Pfeiffer P. Sorbye H. Pyrhonen S. et al (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30: 1755-1762.
121. van Cutsem E. Kohne C. Hitre E. Zaluski J. Chang Chien C. Makhson A. et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360: 1408-1417.
122. van Cutsem E. Peeters M. Siena S. Humblet Y. Hendlisz A. Neyns B. 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: 1658-1664.
123. van Cutsem E. Tabernero J. Lakomy R. Prenen H. Prausova J. Macarulla T. et al (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30: 3499-3506.
124. von Hoff D. Stephenson J. Jr Rosen P. Loesch D. Borad M. Anthony S. et al (2010) Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol 28: 4877-4883.
125. Vrieling A. Voskuil D. Bosma A. Majoor D. van Doorn J. Cats A. et al (2009) Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels. Growth Horm IGF Res 19: 126-135.
126. Walther A. Houlston R. Tomlinson I. (2008) Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut 57: 941-950.
127. Watkins D. Tabernero J. Schmoll H. Trarbach T. Ramos F. Howe J. et al (2011) A randomized phase II/III study of the anti-IGF-1R antibody MK-0646 (dalotuzumab) in combination with cetuximab (Cx) and irinotecan (Ir) in the treatment of chemorefractory metastatic colorectal cancer (mCRC) with wild-type (wt) KRAS status. J Clin Oncol 29(Suppl.): abstract 3501.
128. Wistuba II Gelovani J.G. Jacoby J.J. Davis S.E. Herbst R.S. (2011) Methodological and practical challenges for personalized cancer therapies. Nat Rev Clin Oncol 8: 135-141.
129. Yamauchi M. Morikawa T. Kuchiba A. Imamura Y. Qian Z. Nishihara R. et al (2012) Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 61: 847-854.
130. Yokota T. Ura T. Shibata N. Takahari D. Shitara K. Nomura M. et al (2011) BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer 104: 856-862.
131. Yu M. Grady W. (2012) Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway: novel targeted therapies and advances in the treatment of colorectal cancer. Therap Adv Gastroenterol 5: 319-337.
132. Zhao L. Vogt P. (2008) Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci U S A 105: 2652-2657.
133. Zlobec I. Lugli A. (2008) Prognostic and predictive factors in colorectal cancer. J Clin Pathol 61: 561-569.