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Gastroenterology Research and Practice
Volume 2012 (2012), Article ID 564741, 12 pages
http://dx.doi.org/10.1155/2012/564741
Review Article

How Many Diseases Are Colorectal Cancer?

1Department of Medical Oncology, Christie NHS Foundation Trust, Manchester M20 4BX, UK
2School of Cancer and Imaging Sciences, University of Manchester, Manchester M13 9PL, UK

Received 30 May 2012; Accepted 31 July 2012

Academic Editor: Monique Maas

Copyright © 2012 A. Greystoke and S. A. Mullamitha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. K. Jain, E. A. Hawkes, and D. Cunningham, “Integration of biologic agents with cytotoxic chemotherapy in metastatic colorectal cancer,” Clinical Colorectal Cancer, vol. 10, pp. 245–257, 2011.
  2. S. Barton and C. Swanton, “Recent developments in treatment stratification for metastatic breast cancer,” Drugs, vol. 71, pp. 2099–2113, 2011.
  3. C. Curtis, S. P. Shah, S. F. Chin, et al., “The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups,” Nature, vol. 486, no. 7403, pp. 346–352, 2012.
  4. B. T. Hill and J. Sweetenham, “Clinical implications of the molecular subtypes of diffuse large B-cell lymphoma,” Leukemia & Lymphoma, vol. 53, pp. 763–769, 2012.
  5. A. Custodio, M. Méndez, and M. Provencio, “Targeted therapies for advanced non-small-cell lung cancer: current status and future implications,” Cancer Treatment Reviews, vol. 38, no. 1, pp. 36–53, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Ogino, A. T. Chan, C. S. Fuchs, and E. Giovannucci, “Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field,” Gut, vol. 60, no. 3, pp. 397–411, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Quirke, R. Steele, J. Monson et al., “Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial,” The Lancet, vol. 373, no. 9666, pp. 821–828, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. F. Köckerling, M. A. Reymond, A. Altendorf-Hofmann, O. Dworak, and W. Hohenberger, “Influence of surgery on metachronous distant metastases and survival in rectal cancer,” Journal of Clinical Oncology, vol. 16, no. 1, pp. 324–329, 1998. View at Scopus
  9. W. Van Gijn, C. A. M. Marijnen, I. D. Nagtegaal et al., “Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial,” The Lancet Oncology, vol. 12, no. 6, pp. 575–582, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. W. P. Ceelen, Y. Van Nieuwenhove, and K. Fierens, “Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer,” Cochrane Database of Systematic Reviews, vol. 124, no. 12, pp. 2966–2972, 2009. View at Scopus
  11. T. André, C. Boni, L. Mounedji-Boudiaf et al., “Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer,” The New England Journal of Medicine, vol. 350, no. 23, pp. 2343–2351, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Yamauchi, T. Morikawa, A. Kuchiba et al., “Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum,” Gut, vol. 61, no. 6, pp. 847–854, 2012.
  13. R. Adam, D. G. Haller, G. Poston et al., “Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer-an expert review from the international congress on anti-cancer treatment (ICACT) 2009,” Annals of Oncology, vol. 21, no. 8, pp. 1579–1584, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. M. T. Seymour, T. S. Maughan, J. A. Ledermann et al., “Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial,” Lancet, vol. 370, no. 9582, pp. 143–152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. P. Gervaz, P. Bucher, and P. Morel, “Two colons-two cancers: paradigm shift and clinical implications,” Journal of Surgical Oncology, vol. 88, no. 4, pp. 261–266, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Chauvenet, V. Cottet, C. Lepage, V. Jooste, J. Faivre, and A. M. Bouvier, “Trends in colorectal cancer incidence: a period and birth-cohort analysis in a well-defined French population,” BMC Cancer, vol. 11, article 282, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. I. K. Larsen and F. Bray, “Trends in colorectal cancer incidence in Norway 1962–2006: an interpretation of the temporal patterns by anatomic subsite,” International Journal of Cancer, vol. 126, no. 3, pp. 721–732, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. A. B. Shah, D. Sarfati, T. Blakely, J. Atkinson, and E. R. Dennett, “Trends in colorectal cancer incidence rates in New Zealand, 1981–2004,” ANZ Journal of Surgery, vol. 82, pp. 258–264, 2012.
  19. R. L. Siegel, E. M. Ward, and A. Jemal, “Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992–2008,” Cancer Epidemiology, Biomarkers & Prevention, vol. 21, pp. 411–416, 2012.
  20. K. Derwinger and B. Gustavsson, “Variations in demography and prognosis by colon cancer location,” Anticancer Research, vol. 31, no. 6, pp. 2347–2350, 2011. View at Scopus
  21. J. M. Weiss, P. R. Pfau, E. S. O'Connor et al., “Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results-Medicare data,” Journal of Clinical Oncology, vol. 29, pp. 4401–4409, 2011.
  22. J. Lagergren, W. Ye, and A. Ekbom, “Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis?” Gastroenterology, vol. 121, no. 3, pp. 542–547, 2001. View at Scopus
  23. A. G. Renehan, M. Tyson, M. Egger, R. F. Heller, and M. Zwahlen, “Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies,” The Lancet, vol. 371, no. 9612, pp. 569–578, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. V. W. S. Wong, G. L. H. Wong, S. W. C. Tsang et al., “High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis,” Gut, vol. 60, no. 6, pp. 829–836, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. O. H. Sjo, M. Berg, M. A. Merok et al., “Peritoneal carcinomatosis of colon cancer origin: highest incidence in women and in patients with right-sided tumors,” Journal of Surgical Oncology, vol. 104, no. 7, pp. 792–797, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Hemminki, I. Santi, M. Weires, H. Thomsen, J. Sundquist, and J. L. Bermejo, “Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes,” BMC Cancer, vol. 10, article 688, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. S. B. Edge and C. C. Compton, “The american joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM,” Annals of Surgical Oncology, vol. 17, no. 6, pp. 1471–1474, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. F. T. Bosman, F. Carneiro, R. H. Hruban, and N. D. Theise, WHO Classification of Tumours of the Digestive System, WHO Press, 4th edition, 2010.
  29. J. Verhulst, L. Ferdinande, P. Demetter, and W. Ceelen, “Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis,” Journal of Clinical Pathology, vol. 65, no. 5, pp. 381–388, 2012.
  30. V. Catalano, F. Loupakis, F. Graziano et al., “Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy,” British Journal of Cancer, vol. 100, no. 6, pp. 881–887, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Morikawa, A. Kuchiba, Z. R. Qian et al., “Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer,” The Annals of Surgical Oncology, vol. 19, no. 6, pp. 1944–1953, 2012.
  32. I. Zlobec, F. Molinari, V. Martin et al., “Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients,” World Journal of Gastroenterology, vol. 16, no. 38, pp. 4823–4831, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. E. R. Fearon and B. Vogelstein, “A genetic model for colorectal tumorigenesis,” Cell, vol. 61, no. 5, pp. 759–767, 1990. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Lipson, M. Capelletti, R. Yelensky, et al., “Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies,” Nature Medicine, vol. 18, pp. 382–384, 2012.
  35. F. A. Sinicrope and D. J. Sargent, “Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications,” Clinical Cancer Research, vol. 18, pp. 1506–1512, 2012.
  36. G. A. Calin, R. Gafa, M. G. Tibiletti, et al., “Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: a study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes,” International Journal of Cancer, vol. 89, pp. 230–235, 2000.
  37. M. Yashiro, K. Hirakawa, and C. R. Boland, “Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability,” BMC Cancer, vol. 10, article 303, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. R. A. Kerber, D. W. Neklason, W. S. Samowitz, and R. W. Burt, “Frequency of familial colon cancer and hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in a large population database,” Familial Cancer, vol. 4, no. 3, pp. 239–244, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. W. S. Samowitz, H. Albertsen, J. Herrick et al., “Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer,” Gastroenterology, vol. 129, no. 3, pp. 837–845, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. M. A. Jenkins, S. Hayashi, A. M. O'Shea et al., “Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study,” Gastroenterology, vol. 133, no. 1, pp. 48–56, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. M. T. Parsons, D. D. Buchanan, B. Thompson, J. P. Young, and A. B. Spurdle, “Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification,” Journal of Medical Genetics, vol. 49, pp. 151–157, 2012.
  42. F. A. Sinicrope, N. R. Foster, S. N. Thibodeau et al., “DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy,” Journal of the National Cancer Institute, vol. 103, no. 11, pp. 863–875, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. D. J. Sargent, S. Marsoni, G. Monges et al., “Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer,” Journal of Clinical Oncology, vol. 28, no. 20, pp. 3219–3226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. C. M. Ribic, D. J. Sargent, M. J. Moore et al., “Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer,” The New England Journal of Medicine, vol. 349, no. 3, pp. 247–257, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. A. J. French, D. J. Sargent, L. J. Burgart et al., “Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer,” Clinical Cancer Research, vol. 14, no. 11, pp. 3408–3415, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. G. P. Kim, L. H. Colangelo, H. S. Wieand et al., “Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: A National Cancer Institute-national surgical adjuvant breast and bowel project collaborative study,” Journal of Clinical Oncology, vol. 25, no. 7, pp. 767–772, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. G. Hutchins, K. Southward, K. Handley et al., “Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer,” Journal of Clinical Oncology, vol. 29, no. 10, pp. 1261–1270, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Plaschke, M. Preussler, A. Ziegler, and H. K. Schackert, “Aberrant protein expression and frequent allelic loss of MSH3 in colorectal cancer with low-level microsatellite instability,” The International Journal of Colorectal Disease, vol. 27, no. 7, pp. 911–919, 2012.
  49. M. Pinheiro, T. Ahlquist, S. A. Danielsen et al., “Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin,” BMC Cancer, vol. 10, article 587, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. S. P. Hong, B. S. Min, T. I. Kim et al., “The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer,” European Journal of Cancer, vol. 48, no. 8, pp. 1235–1243, 2012.
  51. D. J. Sargent, S. Marsoni, G. Monges et al., “Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer,” Journal of Clinical Oncology, vol. 28, no. 20, pp. 3219–3226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. B. H. Min, J. M. Bae, E. J. Lee et al., “The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy,” BMC Cancer, vol. 11, article 344, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Jover, T. Nguyen, L. Prezcarbonell et al., “5-fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer,” Gastroenterology, vol. 140, no. 4, pp. 1174–1181, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. J. E. Kim, Y. S. Hong, M. H. Ryu et al., “Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer,” Cancer Science, vol. 102, no. 9, pp. 1706–1711, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. M. M. Bertagnolli, D. Niedzwiecki, C. C. Compton et al., “Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: cancer and leukemia group B protocol 89803,” Journal of Clinical Oncology, vol. 27, no. 11, pp. 1814–1821, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. S. T. Kim, J. Lee, S. H. Park et al., “Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy,” Cancer Chemotherapy and Pharmacology, vol. 66, no. 4, pp. 659–667, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. S. T. Kim, J. Lee, S. H. Park et al., “The effect of DNA mismatch repair (MMR) status on oxaliplatinbased first-line chemotherapy as in recurrent or metastatic colon cancer,” Medical Oncology, vol. 27, no. 4, pp. 1277–1285, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. T. J. Price, J. E. Hardingham, C. K. Lee et al., “Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer,” Journal of Clinical Oncology, vol. 29, no. 19, pp. 2675–2682, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. C. P. Vaughn, S. D. Zobell, L. V. Furtado, C. L. Baker, and W. S. Samowitz, “Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer,” Genes Chromosomes and Cancer, vol. 50, no. 5, pp. 307–312, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. C. S. Karapetis, S. Khambata-Ford, D. J. Jonker et al., “K-ras mutations and benefit from cetuximab in advanced colorectal cancer,” The New England Journal of Medicine, vol. 359, no. 17, pp. 1757–1765, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. R. G. Amado, M. Wolf, M. Peeters et al., “Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 26, no. 10, pp. 1626–1634, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Y. Douillard, S. Siena, J. Cassidy et al., “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,” Journal of Clinical Oncology, vol. 28, no. 31, pp. 4697–4705, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Derer, S. Berger, M. Schlaeth, et al., “Oncogenic KRAS impairs EGFR antibodies' efficiency by C/EBPbeta-dependent suppression of EGFR expression,” Neoplasia, vol. 14, pp. 190–205, 2012.
  64. W. De Roock, B. Claes, D. Bernasconi 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,” The Lancet Oncology, vol. 11, no. 8, pp. 753–762, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Ogino, K. Shima, J. A. Meyerhardt, et al., “Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB, 89803,” Clinical Cancer Research, vol. 18, pp. 890–900, 2012.
  66. X. Liao, T. Morikawa, P. Lochhead et al., “Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review,” Clinical Cancer Research, vol. 18, pp. 2257–2268, 2012.
  67. F. Janku, J. J. Lee, A. M. Tsimberidou et al., “PIK3CA mutations frequently coexist with ras and braf mutations in patients with advanced cancers,” PLoS ONE, vol. 6, no. 7, article e22769, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Velho, C. Oliveira, A. Ferreira et al., “The prevalence of PIK3CA mutations in gastric and colon cancer,” European Journal of Cancer, vol. 41, no. 11, pp. 1649–1654, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Irahara, Y. Baba, K. Nosho et al., “NRAS mutations are rare in colorectal cancer,” Diagnostic Molecular Pathology, vol. 19, no. 3, pp. 157–163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Scartozzi, A. Mandolesi, R. Giampieri et al., “The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab,” Oncologist, vol. 16, no. 1, pp. 53–60, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Inno, M. Di Salvatore, T. Cenci et al., “Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in metastatic colorectal cancer?” Clinical Colorectal Cancer, vol. 10, pp. 325–332, 2011.
  72. C. Bokemeyer, E. V. Cutsem, P. Rougier et al., “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,” European Journal of Cancer, vol. 48, no. 10, pp. 1466–1475, 2012.
  73. T. Yokota, T. Ura, N. Shibata et al., “BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer,” British Journal of Cancer, vol. 104, no. 5, pp. 856–862, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. F. Di Nicolantonio, M. Martini, F. Molinari et al., “Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 26, no. 35, pp. 5705–5712, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Laurent-Puig, A. Cayre, G. Manceau et al., “Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer,” Journal of Clinical Oncology, vol. 27, no. 35, pp. 5924–5930, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. T. S. Maughan, R. A. Adams, C. G. Smith et al., “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,” The Lancet, vol. 377, no. 9783, pp. 2103–2114, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Prahallad, C. Sun, S. Huang et al., “Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR,” Nature, vol. 483, pp. 100–103, 2012.
  78. L. Dal Lago, V. D'Hondt, and A. Awada, “Selected combination therapy with sorafenib: a review of clinical data and perspectives in advanced solid tumors,” Oncologist, vol. 13, no. 8, pp. 845–858, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. V. L. Whitehall, C. Rickman, C. E. Bond et al., “Oncogenic PIK3CA mutations in colorectal cancers and polyps,” International Journal of Cancer, vol. 131, no. 4, pp. 813–820, 2012.
  80. F. Janku, A. M. Tsimberidou, I. Garrido-Laguna et al., “PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors,” Molecular Cancer Therapeutics, vol. 10, no. 3, pp. 558–565, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Young, J. Lyons, A. L. Miller, V. T. Phan, I. R. Alarcón, and F. McCormick, “Ras signaling and therapies,” Advances in Cancer Research, vol. 102, pp. 1–17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: the next generation,” Cell, vol. 144, no. 5, pp. 646–674, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. S. G. Prabhudesai, S. Rekhraj, G. Roberts, A. W. Darzi, and P. Ziprin, “Apoptosis and chemo-resistance in colorectal cancer,” Journal of Surgical Oncology, vol. 96, no. 1, pp. 77–88, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. T. R. Wilson, K. M. McLaughlin, M. McEwan et al., “c-FLIP: a key regulator of colorectal cancer cell death,” Cancer Research, vol. 67, no. 12, pp. 5754–5762, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. D. B. Longley, T. R. Wilson, M. McEwan et al., “c-FLIP inhibits chemotherapy-induced colorectal cancer cell death,” Oncogene, vol. 25, no. 6, pp. 838–848, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. M. Anguiano-Hernandez, A. Chartier, and S. Huerta, “Smac/DIABLO and colon cancer,” Anti-Cancer Agents in Medicinal Chemistry, vol. 7, no. 4, pp. 467–473, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Karasawa, K. Miura, W. Fujibuchi et al., “Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells,” Cancer Science, vol. 100, no. 5, pp. 903–913, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. L. Zhang, L. Q. Pang, Y. Wu, X. Y. Wang, C. Q. Wang, and Y. Fan, “Significance of Bcl-xL in human colon carcinoma,” World Journal of Gastroenterology, vol. 14, no. 19, pp. 3069–3073, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. Y. Pan, R. Xu, M. Peach et al., “Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours,” British Journal of Cancer, vol. 105, no. 12, pp. 1830–1838, 2011.
  90. L. Gandhi, D. R. Camidge, M. R. De Oliveira et al., “Phase I study of navitoclax (ABT-263), a novel bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors,” Journal of Clinical Oncology, vol. 29, no. 7, pp. 909–916, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. B. Leber, F. Geng, J. Kale, and D. W. Andrews, “Drugs targeting Bcl-2 family members as an emerging strategy in cancer,” Expert Reviews in Molecular Medicine, vol. 12, article e28, 2010. View at Scopus
  92. A. G. Letai, “Diagnosing and exploiting cancer's addiction to blocks in apoptosis,” Nature Reviews Cancer, vol. 8, no. 2, pp. 121–132, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. D. O'Mahony, J. C. Morris, C. Quinn et al., “A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy,” Clinical Cancer Research, vol. 13, no. 3, pp. 958–964, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. P. M. Rothwell, M. Wilson, J. F. Price, J. F. Belch, T. W. Meade, and Z. Mehta, “Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials,” Lancet, vol. 379, pp. 1591–1601, 2012.
  95. B. E. Sylvester, D. Huo, A. Khramtsov et al., “Molecular analysis of colorectal tumors within a diverse patient cohort at a single institution,” Clinical Cancer Research, vol. 18, pp. 350–359, 2012.
  96. K. M. Landsbergen, J. B. Prins, H. G. Brunner et al., “Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist's initiative,” Familial Cancer, vol. 11, no. 2, pp. 259–267, 2012.
  97. M. Gerlinger, A. J. Rowan, S. Horswell, et al., “Intratumor heterogeneity and branched evolution revealed by multiregion sequencing,” The New England Journal of Medicine, vol. 366, pp. 883–892, 2012.
  98. A. J. Lee and C. Swanton, “Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics,” Biochemical Pharmacology, vol. 83, pp. 1013–1020, 2012.
  99. S. Oltedal, O. G. Aasprong, J. H. Møller et al., “Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy,” International Journal of Colorectal Disease, vol. 26, pp. 1271–1277, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. K. Balschun, J. Haag, A. K. Wenke, W. von Schonfels, N. T. Schwarz, and C. Rocken, “KRAS, NRAS, PIK3CA exon 20, and BRAF genotypes in synchronous and metachronous primary colorectal cancers diagnostic and therapeutic implications,” Journal of Molecular Diagnostics, vol. 13, pp. 436–445, 2011.
  101. S. Maheswaran, L. V. Sequist, S. Nagrath et al., “Detection of mutations in EGFR in circulating lung-cancer cells,” The New England Journal of Medicine, vol. 359, no. 4, pp. 366–377, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. C. M. Booth, A. H. Calvert, G. Giaccone, M. W. Lobbezoo, L. K. Seymour, and E. A. Eisenhauer, “Endpoints and other considerations in phase I studies of targeted anticancer therapy: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies (MDICT),” European Journal of Cancer, vol. 44, no. 1, pp. 19–24, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. S. L. Ochenduszko and K. Krzemieniecki, “Targeted therapy in advanced colorectal cancer: more data, more questions,” Anti-Cancer Drugs, vol. 21, no. 8, pp. 737–748, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. C. J. A. Punt and J. Tol, “More is less-combining targeted therapies in metastatic colorectal cancer,” Nature Reviews Clinical Oncology, vol. 6, no. 12, pp. 731–733, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. R. A. Adams, A. M. Meade, A. Madi et al., “Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience,” British Journal of Cancer, vol. 100, no. 2, pp. 251–258, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. A. F. C. Okines, S. E. Ashley, D. Cunningham et al., “Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial,” Journal of Clinical Oncology, vol. 28, no. 25, pp. 3945–3950, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. E. B. Larson, A. J. Ellsworth, and J. Oas, “Randomized clinical trials in single patients during a 2-year period,” Journal of the American Medical Association, vol. 270, no. 22, pp. 2708–2712, 1993. View at Publisher · View at Google Scholar · View at Scopus
  108. E. O. Lillie, B. Patay, J. Diamant, B. Issell, E. J. Topol, and N. J. Schork, “The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?” Personalized Medicine, vol. 8, no. 2, pp. 161–173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. D. D. Von Hoff, J. J. Stephenson, P. Rosen et al., “Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers,” Journal of Clinical Oncology, vol. 28, no. 33, pp. 4877–4883, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. J. H. Doroshow, “Selecting systemic cancer therapy one patient at a time: is there a role for molecular profiling of individual patients with advanced solid tumors?” Journal of Clinical Oncology, vol. 28, no. 33, pp. 4869–4871, 2010. View at Publisher · View at Google Scholar · View at Scopus