Thursday, May 04, 2006

From pancreatic cancer to the prevention of heart attack

DailyUpdates from May 4th, 2006: Today we headline with breaking research describing a candidate therapeutic that is able to reduce the drug resistance of pancreatic cancer. In addition we feature news from Icelandic company deCODE Genetics who are moving ahead with the development of a FLAP inhibitor that reduced LTB4 production with the intention of reducing the risk of heart attack. The FDA has now given the green light to commence phase III testing of this promising compound. As usual readers are invited to access today's edition of DailyUpdates in its entirity here

Breaking the resistance of pancreatic cancer to chemotherapy: Failure of cancer chemotherapy is largely caused by multidrug resistance in tumor cells, mediated by ABC transporters that pump many cytostatics out from the cells. This family includes the mammalian P-glycoprotein (MDR1) family and the multidrug resistance-associated protein (MRP). Pancreatic adenocarcinoma is the fifth leading cancer-related cause of death despite its relatively low prevalence, a factor related to its aggressive nature and resistance (see Pancreatic Cancer - Gold Standard Gemcitabine Waiting to be Challenged). Inhibition of the activity of P-glycoprotein efflux pumps offers considerable hope for the treatment of cancer and particularly those that are most highly susceptible to drug resistance. Today's featured journal article presents data on the disiloxanes, synthetic resistance modifiers that suppress not only the multidrug resistance gene but also MRP in various cancer cell lines. The featured study demonstrates that among these compounds, the organosilicon molecule SILA-409 delays tumor growth in a pancreatic cancer xenograft model. This was associated with a reduction in P-glycoprotein expression and an increase in apoptosis. It should be noted that this activity was in the absence of exogenous chemotherapeutics and further studies looking at the combination of such agents with SILA-409 are eagerly awaited.

deCODE advance FLAP inhibitor DG031 towards phase III as an antiinflammatory aimed at reducing myocardial infarction: Cardiovascular disease has been the leading therapeutic category for over two decades and is set to continue its pace of expansion and dominance over the global drugs market. The cardiovascular market has expanded from a value of $60 billion in 1997 to $351.8 billion in 2003. With new drugs in the pipeline, competition in the cardiovascular market has never been greater (see The Cardiovascular Report). deCODE genetics is one company in this arena and yesterday they announced that it has reached an agreement with the FDA on the design of its Phase III clinical trial for DG031, deCODE’s lead developmental compound for the prevention of heart attack. deCODE have previously shown that variants of two genes regulating LTB4 production contribute to risk of heart attack through an increase in plaque inflammation and instability. deCODE thus in-licensed DG031 from Bayer, an inhibitor of the 5-lipoxygenase activating protein, or FLAP. This protein is important for LTB4 synthesis.


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