ABSTRACT
Innovative anticancer strategies are based on the integration of conventional drugs with novel agents selectively targeting molecules directly involved in cell proliferation, angiogenesis and apoptosis. Several tyrosine and serine-threonine kinases have been implicated in the development and progression of the majority of human cancers, becoming potentially relevant therapeutic targets (Gibbs 2000, Levitzki 1999). Different approaches have been developed to block signaling protein kinases activation and/or function in cancer cells, including the generation of monoclonal antibodies, small molecules and second-generation antisense oligonucleotides. Many of these compounds have shown a potent antitumor activity in preclinical models, ability to cooperate with selected class of conventional cytotoxic drugs and activity following oral administration, inhibiting angiogenesis and inducing apoptosis. Such properties may increase therapeutic efficacy and reduce the toxicity, allowing longterm treatment and control of cancer growth. Several of these novel agents are currently under clinical evaluation in cancer patients in early clinical trials or in phase III trials in combination with standard therapeutic regimens. The kinases most extensively studied and exploited for therapeutic purposes are those of the erbB family (epidermal growth factor receptor, EGFR, and erbB-2), as tyrosine kinases, and the cAMP-dependent protein kinase (PKA), as serinethreonine kinase (Tortora & Ciardiello 2000). For these reasons they will be the main object of this chapter.
