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


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.


CONCLUSIONS
Circulating HGF may help identify CRC patients most likely to benefit from anti-epidermal growth factor receptor antibody therapy.
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan yonesaka@sakai.med.kindai.ac.jp.
Kimio
K
Yonesaka
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Taroh
T
Satoh
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Shinya
S
Ueda
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Takeshi
T
Yoshida
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Masayuki
M
Takeda
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Toshio
T
Shimizu
Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan.
Isamu
I
Okamoto
Genome Biology, Kinki University School of Medicine, Osaka, Japan.
Kazuto
K
Nishio
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Takao
T
Tamura
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.
Kazuhiko
K
Nakagawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D005260:Female; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000097:blood
D066258:Amphiregulin; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016211:Transforming Growth Factor alpha; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000068818:Cetuximab
Hepatocyte growth factor; amphiregulin; cetuximab; colorectal cancer; epidermal growth factor receptor; transforming growth factor-α