Signal transduction refers to communication processes used by regulatory molecules to mediate the essential cell processes of growth, differentiation, and survival. Signal transduction elements interact through complex biochemically related networks. Aberrations in signal transduction elements can lead to increased proliferative potential, sustained angiogenesis, tissue invasion and
metastasis, and apoptosis inhibition. Most human
neoplasms have aberrant signal transduction elements. Several compounds that target aberrant signal transduction elements, such as those in the ErbB family of
tyrosine kinase receptors and
mammalian target of rapamycin, are in development. To date, commercially available signal-transduction-targeting compounds include
trastuzumab, a
monoclonal antibody against the
ErbB-2 receptor for the treatment of metastatic
breast cancer overexpressing the ErbB-2 (HER-2) receptor, and
gefitinib, an inhibitor of the
ErbB-1 receptor tyrosine kinase that recently received regulatory approval for the treatment of patients with
non-small cell lung cancer. In contrast to traditional cytotoxic treatments, although signal transduction inhibitors are capable of inducing
tumor regression, particularly in
malignancies that are principally driven by specific target aberrations, preclinical and early clinical investigations suggest that their predominant beneficial effects are growth inhibitory in nature; therefore, new clinical trial designs and evaluation end points may be required to ultimately assess their value. Prospective profiling of patients and
tumors to determine treatment response is also essential to the success of these clinical trials. However, responsiveness to these novel
therapies is dependent on a multitude of factors that ultimately determine the robustness and quality of the downstream response.