ABSTRACT
Available cancer therapies still exhibit very limited value against most solid cancer types, and inevitably result in the development of multidrug-resistant tumors. Because of this, an urgent need exists for therapeutic alternatives to identify compounds with better tolerability at efficacious doses that are directed at defined, disease-relevant molecular targets. The progress made in understanding the molecular basis of mammalian cell transformation has led to unifying concepts of abrogated growth regulation in cancer cells. It is now well recognized that many products of ‘cancer genes’ encode proteins that regulate normal mitogenesis and apoptosis, and that the carcinogenic process is a progressive disorder of signal transduction (Croce, 1987; Alitalo and Schwab, 1988; Bos, 1989; Bishop, 1991; Rabbitts, 1994; Weinberg, 1994). In fact, many of the genes that are mutated or lost in cancer cells, including both oncogenes and tumor suppressor genes, encode proteins that are crucial regulators of intracellular signal transduction (Croce, 1987; Alitalo and Schwab, 1988; Bos, 1989; Bishop, 1991; Rabbitts, 1994; Weinberg, 1994). This conceptual framework has provided a basis for the development of novel anticancer strategies and therapeutic modalities aimed at inhibiting cancer growth either by blocking mitogenic signal transduction or by specifically inducing apoptosis of cancer cells. Although these approaches have not yet been clinically validated, these strategies are likely to identify anticancer agents with fewer undesirable side-effects and greater efficacy than standard chemotherapeutic agents.
