Drugs active against growth factor and oncogene phosphatidylinositol signalling pathways.

Increased knowledge of growth factor and oncogene intracellular signalling presents us with unique opportunities to develop new classes of antiproliferative drugs. The degeneracy of intracellular signalling may allow normal cells to be relatively unaffected by drugs that inhibit just one signalling pathway. Oncoproteins themselves have proved difficult to target and the drugs lack selectivity. More success has come with drugs targeted against other components of signalling pathways. Two examples of such classes of drugs are given. The ether lipid anticancer drugs inhibit intracellular signalling at multiple points; phosphatidylinositol phospholipase C, protein kinase C, intracellular Ca2+ release and phosphatidylinositol-3'-kinase. D-3-deoxy-3-substituted myo-inositols and phosphatidylinositols are a new class of growth inhibitory compounds that appear to act as antagonists of myo-inositol signalling.