Haematologica Reports 2005; 1(issue 8):
77-80[prev][index][next]
Direct and indirect antitumor activity of zoledronic
acid
Massaia M, Mariani S , Pantaleoni F, Muraro M , Peola S, Hwang SY ,
Castella B , Matta G , Foglietta M
Fiore F , Coscia M , Boccadoro M
Divisione di Ematologia dell’Universita’ di Torino and
Laboratorio di Ematologia Oncologica, Centro di Ricerca in Medicina
Sperimentale, Torino, Italy
Zoledronic acid (Zol) is the most potent aminobisphosphonate
currently available to treat bone disease in cancer
patients.1 Zol specifically targets the mevalonate (MVA)
pathway of osteclasts precursors and mature osteoclasts. By
inhibiting the farnesyl pyrophosphate (FPP) synthase, Zol prevents
the generation of FPP and geranylgeranylpyrophosphate (GGPP) that
are essential compounds to prenylate proteins like Ras and Rho
among others.2 The accumulation of unprenylated proteins
in osteoclast precursors and mature osteclasts prevents their
differentiation and activation and ultimately leads to cell death
by apoptosis. By acting upstream on the same pathway targeted by
farnesyl transferase (FTase) and geranylgeranyltransferase (GGTase)
inhibitors (FTI, GGTI), Zol can be considered as a drug impacting
on farnesylation-dependent survival and differentiation pathways.
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