Inhibiteurs de tyrosine-kinase de 2 génération et associations: perspectives

Coiteux, V.
October 2012
Oncologie;Oct2012, Vol. 14 Issue 10/11, p601
Academic Journal
Second-generation tyrosine-kinase inhibitors enable an earlier and higher quality molecular response to be achieved than with imatinib in patients suffering from CML in chronic phase at diagnosis. This implies that in the future a larger number of patients will be candidates for the discontinuation of treatment. However, the majority of patients maintain a detectable residual disease despite their CMR4.5 status.Moreover, in the STIMstudy, more than half the patients who stopped Imatinib after 2 years of CMR, had a molecular relapse. Indeed, it has been shown that quiescent Philadelphia-positive cells recover upon ceasing tyrosine-kinase inhibitors (TKIs). The association of other molecules with TKI, acting by routes other than AbI inhibition, appears to be an interesting and logical option in the goal of eradicating the disease. Several research avenues exist. SMO, CXCR4, STAT5 inhibitors and PEG-IFN act by specific mechanisms which will be detailed here. The PEG-IFN and imatinib combination has shown very promising results, and TKI2 and PEGIFN tests are in progress. No data testing combinations of TKI2 and other molecules on a series of patients has been published to date. We will discuss here the rationale, the issues of this type of therapy and the perspectives in the treatment of CML.


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