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. 2010 Oct 15;127(8):1941-7. doi: 10.1002/ijc.25193.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Insulin-Like Growth Factor I / metabolism*
  • Irinotecan
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • ras Proteins / genetics*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • Irinotecan
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Camptothecin