title: Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan.
abstract: Seventy to 40% of K-RAS wild type colorectal tumors does not seem to benefit from treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies. Recent data suggested that in presence of IGF-1 system, altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. The interaction between IGF-1 expression and K-RAS mutational analysis was tested to verify the ability of IGF-1 to identify a subgroup of patients more likely to benefit from EGFR-targeted antibodies treatment. IGF-1 expression and K-RAS mutational status was assessed in advanced colorectal cancer patients receiving irinotecan/cetuximab. One hundred twelve patients were analyzed. IGF-1 was negative in 30 patients (27%) and overexpressed in the remaining 82 cases (73%). In IGF-1 negative and IGF-1 positive tumors, we observed progressive disease in 9 (30%) and 55 (67%) patients, respectively (p = 0.001). Median progression-free survival was 7.5 mo in patients showing IGF-1 negative tumors and 3 mo for IGF-1 expressing tumors (p = 0.002). Among K-RAS wild type patients, IGF-1 negative and positive tumors showed a partial response to cetuximab-irinotecan in 13 (65%) and 11 (22%) cases, respectively (p = 0.002). Median progression-free survival in IGF-1 negative tumors was 10 mo and 3.2 mo in IGF-1 positive colorectal cancers (p = 0.02). IGF-1 proved to be a possible predictive factor for resistance to anti-EGFR monoclonal antibodies in K-RAS wild type colorectal cancer. Combined IGF-1 and K-RAS analysis may represent an effective strategy for a better selection of responding colorectal cancer patients.
authors.affiliation: Department of Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Chiara
authors.initials: C
authors.lastname: Pierantoni
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.forename: Eva
authors.initials: E
authors.lastname: Galizia
authors.forename: Lucio
authors.initials: L
authors.lastname: Giustini
authors.forename: Rosa Rita
authors.initials: RR
authors.lastname: Silva
authors.forename: Renato
authors.initials: R
authors.lastname: Bisonni
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Simona
authors.initials: S
authors.lastname: Biagetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Menzo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D007334:Insulin-Like Growth Factor I; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin