Multiple-target drugs: inhibitors of heat shock protein 90 and of histone deacetylase.
In spite of the improvement of conventional medical therapy for cancer treatment, the impact on cancer related mortality in the last ten years has been modest especially for advanced disease in adults. On the other hand, understanding of molecular events underlining tumor development lead to the definition of new molecular targets for novel anti-tumor therapeutical approaches. On this regard, several biotechnology products selected by academic as well as industrial research are currently in clinical trials. Epigenetics as well as post-translational modifications of proteins are emerging as novel attractive targets for anticancer therapy. In addition, the heterogeneity of tumor cells within a selected neoplastic lesions as well as the redundancy of proliferative and survival pathways present in cancer cells favor the development of single drugs that are able to affect multiple pathways. Inhibitors of heat shock protein 90 and of histone deacetylase are two novel classes of multi-target agents that entered recently in clinical studies. This review will focus on the most important issues in the development of both these classes of agents.
Budillon
A
A
Experimental Pharmacology Unit, Department of Experimental Oncology, National Cancer Institute Fondazione G. Pascale, Naples, Italy. budillon@fondazionepascale.it
Bruzzese
F
F
Di Gennaro
E
E
Caraglia
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors