AuthOr’s VIew AuthOr’s VIew

One major trend in modern cancer ther-apy is to develop drugs that target a spe-cific signaling pathway, aimed at achieving the selective killing of cancer cells with reduced side effects for normal tissues. Examples of this trend include inhibitors of the oncogenic protein kinases, ERBB2 (HER2) and BCR-ABL, which interfere with hyperactivated survival signaling. Such selective (“clean”) inhibitors are ini-tially quite effective. However, the long-term use of these compounds is often limited by the acquisition of resistance, either upon the mutation of drug targets or by other bypass mechanisms that cancer cells develop in response to this selective pressure. In contrast, pleiotropic (“dirty”) drugs simultaneously affect several regula-tory pathways that are requied for the sur-vival of cancer cells, thus being less prone to generate resistance. This notion has led to the search for new pleiotropic agents that efficiency and specifically eliminate cancer cells. Such novel drugs are exempli-fied by inhibitors of protein chaperons and by compounds that influence the chroma-tin status