Abstract
In the past decade, the standard of care for advanced colorectal cancer has been in a state of flux with the introduction of new agents in the treatment of stage IV disease; however, the 5-year survival rate for advanced disease remains low. Investigators are trying to identify biomarkers that may be predictive and/or prognostic for these agents and thereby improve patient outcomes. This article discusses recent discoveries that have identified the importance of KRAS mutational status in predicting responses to epidermal growth factor receptor-targeting antibodies (cetuximab and panitumumab) in the management of metastatic colon cancer.
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References and Recommended Reading
Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2008. CA Cancer J Clin 2008, 58:71–96.
Wolpin BM, Mayer RJ: Systemic treatment of colorectal cancer. Gastroenterology 2008, 134:1296–1310.
Malumbres M, Barbacid M: RAS oncogenes: the first 30 years. Nat Rev Cancer 2003, 3:459–465.
Schubbert S, Shannon K, Bollag G: Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007, 7:295–308.
Downward J: Targeting RAS signaling pathways in cancer therapy. Nat Rev Cancer 2003, 3:11–22.
Shaw RJ, Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006, 441:424–430.
Zhu D, Keohavong P, Finkelstein SD, et al.: K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients. Cancer Res 1997, 57:2485–2492.
Andreyev HJ, Norman AR, Cunningham D, et al.: Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 2001, 85:692–696.
Amado RG, Wolf M, Peeters M, et al.: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008, 26:1626–1634.
Karapetis CS, Khambata-Ford S, Jonker DJ, et al.: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008, 359:1757–1765.
Esteller M, Gonzalez S, Risques RA, et al.: K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol 2001, 19:299–304.
Barault L, Veyrie N, Jooste V, et al.: Mutations in the RASMAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer 2008, 122:2255–2259.
Van Cutsem E, Köhne CH, Hitre E, et al.: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009, 360:1408–1417.
Bokemeyer C, Bondarenko I, Makhson A, et al.: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009, 27:663–671.
Hecht JR, Mitchell E, Chidiac T, et al.: A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009, 27:672–680.
Tol J, Koopman M, Cats A, et al.: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009, 360:563–572.
Allegra CJ, Jessup JM, Somerfield MR, et al.: 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 (Epub ahead of print).
Nollau P, Wagener C: Methods for detection of point mutations: performance and quality assessment. Clin Chem 1997, 43:1114–1128.
Gallegos Ruiz MI, Floor K, Rijmen F, et al.: EGFR and K-ras mutation analysis in non-small cell lung cancer: comparison of paraffin embedded versus frozen specimens. Cell Oncol 2007, 29:257–264.
Jimeno A, Messersmith WA, Hirsch FR, et al.: KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J Clin Oncol 2009, 27:1130–1136.
Santini D, Loupakis F, Vincenzi B, et al.: High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist 2008, 13:1270–1275.
Di Nicolantonio F, Martini M, Molinari F, et al.: Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008, 26:5705–5712.
Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al.: Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007, 67:2643–2648.
De Roock W, Piessevaux H, De Schutter J, et al.: KRAS wild type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008, 19:508–515.
Finocchiaro G, Cappuzzo F, Janne PA, et al.: EGFR, HER2 and Kras as predictive factors for cetuximab sensitivity in colorectal cancer [abstract]. J Clin Oncol 2007, 25(Suppl):4021.
Di Fiore F, Blanchard F, Charbonnier F, et al.: Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer 2007, 96:1166–1169.
Khambata-Ford S, Garrett CR, Meropol NJ, et al.: Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007, 25:3230–3237.
Lievre A, Bachet JB, Boige V, et al.: KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008, 26:374–379
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Leong, S., Eckhardt, S.G., Jimeno, A. et al. The importance of KRAS status in managing metastatic colorectal cancer. Curr colorectal cancer rep 5, 129–134 (2009). https://doi.org/10.1007/s11888-009-0019-4
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DOI: https://doi.org/10.1007/s11888-009-0019-4