Oncogene Addiction Clinical Evidence

There is clinical evidence that oncogene addiction exists. This could be seen in CML.  CML is referred as Chronic myeloid leukemia. This involves chromosome 22 and an abnormality. A translocation event happens between chromosome 9 and chromosome 22 and there are RAG’s. When there is a mutation it causes RAG to cut some of the Abl gene and more of the Bcr gene. When combined it forms a changed chromosome 22 (Philadelphia chromosome).  CML is essentially driven by the BCR-ABL mutant oncogene so it is addicted. This was demonstrated in patients through the clinical responses attained with the kinase inhibitor imatinb, which targets BCR-ABL. It is further supported by genetic mechanisms of resistance that vastly led to reactivation of BCR-ABL kinase activity. Another example is antiandrogens and using them for the treatment of prostate cancers, which are known to be ‘lineage addicted’ to AR and have recurrent AR amplifications or mutations upon resistance to first line therapeutic techniques.