Affiliation: Surgical Oncology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Metastasization is an undesirable process in cancer development and may represent the most critical factor in deciding patient prognosis. Organ specificity of the metastasis process suggests the importance of the paracrine factors: one of the most potent paracrine regulators of tumor cell migration is hepatocyte growth factor/scatter factor (HGF/SF). Because the liver-specific growth factor is HGF, its receptor c-Met expression might play a critical role in metastasization to the liver. Activation of HGF/c-Met signaling has been shown to promote cancer cell invasiveness and trigger metastasis though direct involvement of the angiogenic pathway. Given the importance of aberrant HGF/c-Met signaling, several different therapeutic strategies aimed at inhibiting the pathway have been developed and are currently being evaluated in clinical trials. Among these agents, NK4 and AM102 were introduced as HGF inhibitors, and PHA-665752 and Su11274 as c-Met inhibitors and are under study in clinical trials. Further, clinical experience-based study to apply the accumulation of biological knowledge concerning HGF/c-Met to the surgical field is presented.