Medication CML Chronic Myeloid Leukemia

"Treatment of Chronic myeloid leukemia represents one of cancer’s success stories. Deregulated tyrosine kinase activity of the BCR-ABL fusion protein has been established as the causative molecular event in CML. The drug Imatinib has revolutionized the treatment of CML and has become the gold standard of care in CML for it is a highly targeted BCR-ABL tyrosine kinase inhibitor (TKI) that induces complete hematologic response and sustained complete cytogenetic response in more than 80% of patients. Despite of such impressive response rates achieved with imatinib, some patients in the advanced stage of CML frequently obtain less modest responses. It may be due to resistance to the wonder drug imatinib, which in turn results in failure of treatment, even after large dose escalation. This has led to the development of novel treatment strategies which are currently being investigated in newly diagnosed CML and include upfront treatment with the next-generation tyrosine kinase inhibitors, such as dasatinib, nilotinib, or bosutinib, which also target the BCR-ABL but with increased in vitro potency as compared to imatinib, and possibly with a reduced potential for resistance. Such newer agents and combination approaches can improve treatment responses as compared with standard imatinib treatment. In addition, many other protein kinases implicated in signaling transduction downstream BCR-ABL also play critical roles in the pathogenesis of CML, thereby representing potential therapeutic targets as revealed from several clinical studies. While in many other cases, the CML cells develop mutations, which is a change in the amino acid sequence of the BCR-ABL oncogene, the most dangerous amongst them is the T315I mutation, which makes them resistant to the current targeted therapies (imatinib, dasatinib, and nilotinib). Newer drugs that work against T315I mutant cells are now being tested. Ponatinib, is one such pan-BCR-ABL inhibitor, which has shown ongoing strong efficacy in its continuing Phase 1 trial in treatment of the T315I mutation CML, as well as all other known mutations. Still other novel drugs in the pipeline, the farnesyl transferase inhibitors, such as lonafarnib and tipifarnib, seem to have some activity against CML and patients may respond favourably when such drugs are combined with imatinib. With many such novel drugs under development and many more in the pipe line, some of such drugs which are in various phases of clinical trials are being discussed."
Extract of Novel Agents In CML Therapy: Tyrosine Kinase Inhibitors and Beyond

ARTiCLES

Novel Agents In CML Therapy: Tyrosine Kinase Inhibitors and Beyond
July 3, 2012, WebmedCentral

On the Horizon: Novel Inhibitors for Hematologic Malignancies
June 13, 2012, Onc Live

Novel agents in CML therapy: tyrosine kinase inhibitors and beyond
2008, PublMed

See also
Imatinib
        Dasatinib
             Nilotinib
                     Bosutinib
                          Bafetinib
                               Danusertib
                                     Ponatinib
                                         Rebastinib
                                              Omacetaxine
                                                         Radotinib