Velcade (Molecule of the Month for June 2007)
Velcade is the first therapeutic proteasome inhibitor to be tested in humans. It is the best studied of a next generation of anti-myeloma drugs, and is being studied for other hematologic cancers and solid tumors. Myeloma is debilitating form of bone marrow cancer. It is currently incurable and is a cancer of the plasma cells found in the bone marrow. The incidence increasing faster than any other cancer in Western world - up 30% in 30 years, there are 20,000 myeloma patients in the UK at any one time.
The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity. In normal cells, the proteasome regulates protein expression and function by degradation of ubiquinated proteins, and also cleanses the cell of abnormal or misfolded proteins. Clinical and preclinical data support a role in maintaining the immortal phenotype of myeloma cells, and cell-culture and xenograft data support a similar function in solid tumor cancers. While multiple mechanisms are likely to be involved, proteasome inhibition may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways.
The National Institute for Health and Clinical Excellence is recommending multiple myeloma patients in Wales and England should get Velcade on the NHS. But it said the NHS should pay for the drug, which costs about £18,000 per patient, only when it worked. Under the terms of the NICE recommendation, patients showing a full or partial response to the drug after a maximum of four cycles of treatment would be kept on it, with the treatment funded by the NHS. However, patients showing minimal or no response would be taken off it - and the costs would be refunded by the manufacturer.
Formal Chemical Name (IUPAC)
Update by Karl Harrison
(Molecule of the Month for June 2007 )