Interesting science behind the drug I am on

For those of you not interested in things chemical and biological...I suggest you skip this entry.

One of the amazing developments over the last 20 years in biology is our understanding of genes and DNA and our ability to easily sequence the DNA of genes. In the late 1960s, I was doing research with Dr. Jack Remington, a world expert on toxoplasma gondii at Stanford and it took us months just to separate the DNA in different strains. Researchers were just beginning to discover that a change of one amino acid in a protein (caused by a mutation in a gene) could make the difference between a normal person and a person with sickle cell anemia or a normal child and a severely retarded one with PKU.

Fast forward to today, using sequencing techniques, scientists are discovering that some cancer cells can be characterized by genes that have mutated and don't work properly and cause the cell to divide prolifically. Discovering drugs that can attack the products of these mutated genes and stop the cells from dividing are leading to treatments that cure or hold some cancers in check.

For example, chronic myelogenous leukemia (CML) is caused by a single genetic change that makes a gene keep producing a specific enzyme, a kinase, that after a cascade of chemical reactions, causes the cells to continue to divide. A drug called "Gleevec" has been developed that binds to the kinase. People take Gleevec for their lives and their CML doesn't return. In about 5% of the CML cases, the cells become resistant to Gleevec, but scientists have discovered why and have developed two other drugs that work to block the kinase when this happens.

So what about melanoma? In the last 20 years, there have been no therapeutic advances in its treatment and half of the patients with metastatic melanoma die within 6 months. Scientists have discovered that half of the people with melanoma have a mutation in the BRAF gene in their tumor cells. The drug that I am on, a BRAF inhibitor, targets the product of that mutation. In Stage I and II trials, tumors shrank in 80% of the cases (mine have shrunk). Unfortunately most of the patients relapsed within a year. (The hope for me is if I relapse to where I was before the trial, I will have random tumors that can be treated with radiation or that my own immune system can respond with the help of some of the new immune enhancing drugs. )

The thinking is that the melanoma cells became resistant to the drug by keeping the drug from binding to BRAF or by switching to a different driver mutation. Research is very actively trying to develop back-up drugs. There is one trial going with a BRAF inhibitor and one that targets the back-up pathway.

So you can see that research is at a critical stage right now. I just need to hold on for two or three more years!!

(PS. Donations to the Melanoma Research Foundation at my website ( http://www.firstgiving.com/mollybloomfield) have reached 25% of my goal of $5000 by the Holidays)