title: Bevacizumab-based treatment in colorectal cancer with a NRAS Q61K mutation.
abstract: Despite development of new therapies, metastatic colorectal cancer (mCRC) largely remains an incurable disease. Approximately 2-6% of colorectal cancers harbor NRAS mutations. The anti-VEGF antibody bevacizumab is a backbone of most therapeutic regimens; however, biomarkers predicting its activity are not known. We report two cases of mCRC with a Q61K NRAS mutation that had a favorable response to bevacizumab and the histone deacetylase inhibitor valproic acid. In contrast, none of ten patients with wild-type NRAS or unknown NRAS status and mutated KRAS (NRAS and KRAS mutations are mutually exclusive) responded to the same regimen. These results suggest that NRAS mutation merits further investigation as a potential biomarker predicting the efficacy of bevacizumab-based treatment.
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 0455, Houston, TX, 77030, USA. fjanku@mdanderson.org.
authors: Filip
authors: F
authors: Janku
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 0455, Houston, TX, 77030, USA.
authors: Jennifer J
authors: JJ
authors: Wheler
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 0455, Houston, TX, 77030, USA.
authors: David S
authors: DS
authors: Hong
authors: Moores Cancer Center, The University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093, USA.
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D000068258:Bevacizumab; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
references: Mol Cancer Ther. 2008 Apr;7(4):737-9
references: 18375819
references: Nat Rev Cancer. 2003 Jun;3(6):459-65
references: 12778136
references: Nat Rev Cancer. 2001 Dec;1(3):194-202
references: 11902574
references: Mol Cell Biol. 2002 Mar;22(5):1589-606
references: 11839824
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50
references: 20952405
references: Nat Genet. 2008 May;40(5):600-8
references: 18372904
references: N Engl J Med. 2009 Apr 2;360(14):1408-17
references: 19339720
references: Clin Cancer Res. 2011 Jan 15;17(2):229-35
references: 20975100
references: Cancer Res. 2004 Sep 15;64(18):6626-34
references: 15374977
references: Mol Cancer Ther. 2007 Aug;6(8):2209-19
references: 17699718
references: Cancer Res. 2006 Sep 1;66(17):8814-21
references: 16951198
references: CNS Drug Rev. 2003 Summer;9(2):199-216
references: 12847559
references: J Clin Oncol. 2008 Apr 20;26(12):2013-9
references: 18421054
references: Cancer Cell. 2006 Jan;9(1):33-44
references: 16413470
references: CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36
references: 21685461
references: Nature. 2006 Jan 19;439(7074):358-62
references: 16273091
references: Nat Med. 2001 Apr;7(4):437-43
references: 11283670
references: Lancet Oncol. 2010 Aug;11(8):753-62
references: 20619739
references: N Engl J Med. 2006 Dec 14;355(24):2542-50
references: 17167137
references: N Engl J Med. 2004 Jun 3;350(23):2335-42
references: 15175435
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):57-62
references: 16371460
references: PLoS One. 2011;6(7):e22769
references: 21829508
references: J Clin Oncol. 2001 Feb 1;19(3):851-6
references: 11157039