Battling the hematological malignancies: the 200 years’ war
Lichtman MA. Battling the hematological malignancies: the 200 years’ war. Oncologist. 2008 Feb;13(2):126-38. PMID: 18305057
A clearly written historical review and perspective on current research by Marshall Lichtman of the University of Rochester Medical Center.
Professor Marshall applies a systems approach to drug development, employing a nuanced interpretation of the imatinib (Glivec) story as a case study:
"When one has stratified the blood cancers into phenotypes and genotypes, the number of patients amenable to a specific oncogene- or oncoprotein-targeted therapy becomes relatively small. This situation is unattractive for pharmaceutical companies that may need to invest hundreds of millions of dollars into the effort to develop a drug. For a pharmaceutical company, the greater the specificity of the drug, the fewer the number of future users. Today, most drugs can be used for several blood cancers and for cancers of other tissues. To move to more focused and, presumably, more effective and less toxic drugs, collaboration among governmental agencies, such as the National Institutes of Health, the pharmaceutical and biotechnology industries, and academic health centers (research-intensive medical schools, research institutes, research hospitals) needs to be further enhanced.
"There are incentives for companies to pursue drugs with an apparently small market. For example, the development of imatinib mesylate may have done more than advance the treatment of CML; it may have caused pharmaceutical companies to have second thoughts about developing new drugs for uncommon cancers. The pharmaceutical company involved (Ciba-Geigy, later Novartis) was looking for a drug to block a tyrosine kinase (platelet-derived growth factor receptor) potentially involved in atherosclerosis, a very large market, but was forced to aggressively manufacture imatinib mesylate because of the demands of patients with CML, a very small market, and in the end did (very) well by doing good, because of pricing, because of the fact that the drug is required indefinitely, and because of the drug’s ability to cause the remission of a gastrointestinal stromal tumor, which effectively doubled the target patient population. The latter event is another example of how drug development in the hematological malignancies continues to provide the path to therapy of other types of cancer."
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