The very early intuition by Paget about the molecular features of metastasis
has been observed in the field of therapeutic opportunities only in the last few years
with the development of targeted therapy. However, to date, the diagnosis of metastases
is associated in the majority of cases with the loss of any therapeutic hope. According to
present knowledge, metastatic spread is considered a part of a long process in which
tumor cells gain new properties regarding their cellular function, including invasion and
adaptive survival. This gain of function is based on the expression of new molecular
markers that may be potential therapeutic targets in blocking tumor diffusion. The
epidermal growth receptor family (ErbB) comprises four members that are frequently
upregulated in advanced tumor stages and have been associated with the metastatic
potential of several tumors. Several inhibitors specific for one ErbB receptor have been
demonstrated to be effective antitumor agents in primary cancer, but their utilization is
restricted to ErbB-overexpressing tumors and limited by toxicity problems, drug
resistance and molecular desensitization. However, new studies indicate that ErbB
inhibitors may provide a much-needed therapeutic option, mainly for patients with
metastases. In order to illustrate the potential of ErbB family members as therapeutic
targets in blocking metastases, we summarize the latest molecular evidence and the
results of clinical trials.
Keywords: Cancer metastasis, clinical trials, EGF, epidermal growth factor,
HER2, targeted therapy, tumor invasion, trastuzumab, tyrosine kinases.
