CONICET | Buscador de Institutos y Recursos Humanos

Targeted therapy is a strategy of anticancer treatment that aims to interfere with processes of tumorigenesis, cancer progression and metastasis by selectively affecting ey molecules of tumor cells. Targeted therapies are directed to small molecules participating in different mechanisms that control cell survival through cellular proteins or signalling pathways. Targeted therapies may offer enhanced efficacy, enhanced selectivity, and less toxicity. However, targeting selective molecules and pathways often induces the activation of redundant mechanisms and enhances the emergence of resistant cells due to selective pressure. This is one of the reasons why the effects of targeted agents are not durable when used alone, and often result in drug resistance and clinical relapse. Novel treatments require the investigation of mechanisms of action and synergy ofkcombination treatments to enhance the role of the targeted pharmacological agents. Evaluating combinations of targeted drugs, including investigational agents, are an essential part of this effort. An interesting example is represented by Bortezomib, a drug currently effective as single agent in multiple myeloma and mantle cell lymphoma. Bortezomib is a proteasome inhibitor that selectively triggers apoptosis in various types of neoplastic cells. It has been tested in a wide variety of solid tumors but has generally been ineffective as monotherapy . However Bortezomib has shown increased activity when combined with several novel targeted agents including protein deacetylase inhibitors, inase inhibitors, farnesyltransferase inhibitors, HSP-90 inhibitors, pan-Bcl-2 family inhibitors, and other classes of targeted inhibitors. Thus, Bortezomib in combination with novel targeted therapies increase antitumor activity and overcome specific cellular antiapoptotic mechanisms.