Studies Show Gene Expression Activity in Leukemia Cells
Two studies, both in the August 5 New England Journal of Medicine, offer new insights to some of the underlying mechanisms of acute lymphoblastic leukemia (ALL), a leading form of cancer among children. The first study, by researchers at St. Jude Children's Research Hospital in Tennessee; Erasmus University - Sophia Children's Hospital in Rotterdam, the Netherlands; and the COALL cooperative group in Germany; identified sets of genes that are differentially expressed in leukemia cells resistant to each of four antileukemia drugs tested, and also showed that the pattern of expression of these genes was related to overall patient outcomes. The second study, by researchers at the National Cancer Institute (NCI), found that the loss of a key protein (Smad3) is specific to one form of childhood leukemia, but not to other pediatric and adult leukemias.
Dr. William Evans of St. Jude and colleagues compared total gene expression of leukemia cells taken from 173 ALL patients and grouped the samples that exhibited resistance to one of four drugs: prednisolone, vincristine, asparaginase, or daunorubicin. They found 124 genes and 28 cDNA (potential genes) that are differently expressed in drug-resistant cells. "Interestingly, only three of those genes had previously been associated with drug resistance," said Dr. Evans, "so there are unexpected cellular mechanisms at work." There was also little gene overlap among the drugs, and no gene was present on all four lists. The expression profiles for drug resistance were similar across different ALL subtypes, indicating that the mechanism of disease resistance is independent of the molecular cause of the leukemia. Read more
Refashioning the Clinical Trials System for a New Era of Opportunity
Robust, extensive, formidable: All of these terms aptly describe the system of clinical trials that underpins clinical cancer research in the United States. Our cancer clinical trial system is, in many respects, the envy of most research establishments; it has helped to save and/or extend the lives of millions of people in the United States and, no doubt, around the world.
It is also clear, however, that our clinical trials system has a number of shortcomings that hinder its effectiveness and limit our ability to make the rapid progress I believe can be achieved in this age of advanced technology and improved understanding of how various cancers operate at the genetic and molecular level. There is, for example, a significant degree of duplication of effort and fragmentation in the clinical trial system, which wastes resources and slows the clinical trials enterprise. In addition, many trials take many years and resources to complete, only to produce equivocal results. There are also problems with poor patient participation, inadequate reimbursement of trial costs, and complex regulatory requirements. Finally, and perhaps most importantly, there is a lack of a widely accepted bioinformatics platform to support a national clinical trials effort. Read more