Exploiting cancer cell cycling for selective protection of normal cells

Chemotherapy of cancer is limited by its toxicity to normal cells. On the b asis of discoveries in signal transduction and cell cycle regulation, novel mechanism-based therapeutics are being developed. Although these cell cycl e modulators were designed to target cancer cells, some of them can also be applied for a different purpose, i.e., to protect normal cells against the lethality of chemotherapy. Loss of sensitivity of cancer cells to cell cyc le inhibitors can be exploited for selective protection of normal cells tha t retain this response. Indeed, inhibition of redundant or overactivated pa thways (e.g., growth factor-activated pathways) or stimulation of absent pa thways in cancer cells (e.g, p53, Rb, and p16) may not arrest cycling of ca ncer cells. But growth arrest of normal cells will then permit selective ki lling of cancer cells by cycle-dependent chemotherapy.