Wonder Drugs, and Sequencing Tumor Mutations
A reminder of a point stressed during June’s Perrin conference on asbestos science. There, the experts stressed the fact that gene sequencing data increasingly will be part of the medical profile for some persons stricken by mesothelioma. That means that the record for some future asbestos causation trials will include medical records with data on the specific mutation(s) found in the tumor tissue when compared to that person’s normal tissue.
Why is sequencing being done? Sequencing is done because pharma today is able to deliver occasional "wonder drugs" that will block the impact of a mutation by, for example, suppressing or activating one or more enzymes or proteins.
A prime example of the wonder drugs is Gleevec. Technically known as imatinib, it is a true wonder drug for persons with tumors driven by the "Philadelphia" mutation that produces some of the increasing numbers of chronic myeloid leukemias. That specific form of CML is now known in shorthand terms as Ph+ CML. The abbreviations mean Philadelphia mutation positive chronic myeloid leukemia.
What does a wonder drug do? It targets the consequence of the mutation. In the case of the PH+ CML, the mutation causes constant activation of the process by which proteins are stimulated to produce, thus leading to excess production of myeloid cells. It’s that "simple" – stop the production of the problem protein. It’s sort of like blocking a tube of water from filling a water balloon – the point is to interrupt the path that is producing the tumor. In more technical terms, Wikipedia nicely explains Gleevec as follows:
"Like all tyrosine-kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme, in this case BCR-Abl, from phosphorylating subsequent proteins and initiating the signaling cascade necessary for cancer development, thus preventing the growth of cancer cells and leading to their death by apoptosis. Because the BCR-Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, imatinib works as a form of targeted therapy—only cancer cells are killed through the drug’s action. In this regard, imatinib was one of the first cancer therapies to show the potential for such targeted action, and is often cited as a paradigm for research in cancer therapeutics."