Circulating hepatocyte growth factor is correlated with resistance to cetuximab in metastatic colorectal cancer

Anticancer Res. 2015 Mar;35(3):1683-9.

Abstract

Background/aim: The epidermal growth factor family (EGF) has been suggested to influence the sensitivity to anti-epidermal growth factor receptor therapy. We examined the correlation between circulating levels of the epidermal growth factors amphiregulin and transforming growth factor-α (TGF-α) and the MET ligand hepatocyte growth factor and sensitivity to the anti-epidermal growth factor receptor antibody in colorectal cancer (CRC) patients.

Materials and methods: Plasma levels of each ligand were measured by enzyme-linked immunosorbent assay in 51 patients with wild-type KRAS CRC.

Results: Patients with high hepatocyte growth factor (HGF) levels had a significantly lower disease control rate (DCR) and shorter median progression-free survival (PFS) and overall survival (OS) than those with low expression levels. Amphiregulin was correlated with objective response rate (ORR) but not with PFS or OS. Cetuximab response and survival were not associated with TGF-α.

Conclusion: Circulating HGF may help identify CRC patients most likely to benefit from anti-epidermal growth factor receptor antibody therapy.

Keywords: Hepatocyte growth factor; amphiregulin; cetuximab; colorectal cancer; epidermal growth factor receptor; transforming growth factor-α.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amphiregulin / blood
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Cetuximab
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Drug Resistance, Neoplasm
  • Female
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Hepatocyte Growth Factor / blood*
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-met / physiology
  • Transforming Growth Factor alpha / blood

Substances

  • Amphiregulin
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Transforming Growth Factor alpha
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Cetuximab