Tuesday, July 3, 2007
Every now and again I like to throw out the old paradigms and put in some new. Geneticists love this......The So Called "Paradigm Shift"
Back in 2005 this was done with Marfan's disease. It is an example I use to teach my students that what they may have learned is wrong. It is wrong because medical teaching is only built on science that has a very limited set of knowns and an immense set of unknowns.
This paradigm shift is already in the making.
The classical model of how a cancer develops is called the "two-hit" hypothesis. It states that in order to have uncontrolled growth of cells i.e. cancer, you need two hits to genes. Mostly you have to have at least 2 mutations. Sometimes you activate a gene by mutation and other times you may silence the genes. For the last 30 years the view of cancer is a very geno-centric. Just look at our so called targeted therapies. They block single gene proteins. Guess what. Even when these elegantly designed therapies are administered some cancers develop resistance. Why? I thought that the genes mutated were what caused the cancer. Shouldn't this wonderfully targeted therapy work for all cancers with this gene mutation? The answer is the same as for this question...
Shouldn't all persons with sickle cell have the exact same disease prognosis and complications? NO....no gene or genes are an island!
This new paradigm states just that. It says cancer is the result of 1000s of genes and the chromosome is really the master here. Screw up enough chromosomes and you get cancer. Let's face it. It is now known that gene expression arrays predict the response to chemo better than a single gene or even a microscopic cell type. This indicates that massive gene expression changes similar to those you may get from a chromosomal anomaly could be at play. Is this true? And what role will it play in the personalized therapy for cancers?
The Sherpa Says: This is very likely to be true. That is not to diminish the role of those rare cancers that are uniquely mono/bi-genic. This will lead to better therapies and earlier detection. It could eventually mean that every single case of cancer will truly be personalized and will require personalized medicine in the truest sense.......