Research from Alfred Hospital in the area of myeloma therapy published

03-27-2007

Current study results from the report, "Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma," have been published. "Clinical studies have suggested that bisphosphonates may prolong the survival of sub-sets of myeloma patients. Newer nitrogen containing bisphosphonates such as zoledronate act, at least in part, by inhibiting farnesyl diphosphate synthase and subsequent protein prenylation, furthermore, limited data suggests that zoledronate exerts a direct anti-tumour effect against human myeloma cell lines," researchers in Melbourne, Australia report.

"We therefore investigated the anti-myeloma potential of zoledronate in comparison to, and in combination with, two other inhibitors of the mevalonate pathway: the HMGCoA reductase inhibitor fluvastatin and the farnesyl transferase inhibitor SCH66336. We found that fluvastatin was able to inhibit the proliferation of myeloma cells more effectively than zoledronate or SCH66336 and that combinations of zoledronate and fluvastatin, but not zoledronate and SCH66336 acted synergistically. Our data indicated that the anti-proliferative effect of mevalonate pathway inhibitors is mediated principally via prevention of geranylgeranylation and is the result of both cell cycle arrest and apoptosis induction. Microarray and quantitative real-time PCR analyses further demonstrated that genes related to apoptosis, cell cycle control, and the mevalonate pathway were particularly affected by zoledronate and fluvastatin, and that some of these genetic effects were synergistic," wrote C. Baulch-Brown and colleagues, Alfred Hospital.

The researchers concluded: "We conclude that the mechanisms of geranylgeranylation inhibition mediated anti-myeloma effects warrant further evaluation and may provide novel targets for future therapeutic development."

Baulch-Brown and colleagues published their study in Leukemia Research (Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leukemia Research, 2007;31(3):341-52).

For additional information, contact C. Baulch-Brown, Myeloma Research Group, Dept. of Clinical Haematology and Bone Marrow Transplantation, Ground Floor, South Block, Alfred Hospital, Commercial Road, Melbourne, Vic 3004, Australia.

Publisher contact information for the journal Leukemia Research is: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.