Small molecule signal transduction inhibitors for the treatment of solid tumors.

A greater understanding of the pathogenesis of malignancy has led to the development of novel therapies designed to target aberrant molecular pathways that characterize and distinguish cancer cells from normal tissue. Small molecules are being designed to interfere with specific steps along the deregulated signaling cascade from the cytoplasmic membrane to the nucleus. Viable targets include growth factor receptors and their downstream second messengers, modulators of the cell cycle or apoptosis, regulators of protein trafficking and degradation, and transcription regulators. This review will discuss the small molecule signal transduction inhibitors in various stages of development and address the strategic issues relating to clinical trial design with these novel targeted agents.