Emerging drugs for chronic myeloid leukemia.
BACKGROUND
The deregulated tyrosine kinase activity of BCR-ABL has been demonstrated to be necessary and sufficient to maintain leukemia phenotype of chronic myeloid leukemia (CML) which, therefore, represents a unique model for the development of molecular targeted therapy and the first disease in which the tyrosine kinase inhibitors (TKIs) completely changed the therapeutical approach. The impressive results of TKIs in this model have been overshadowed by the development of clinical resistance.


METHODS
This review focuses on clinical results with imatinib therapy and second generation TKIs. Furthermore, a summary of the guidelines for the management of TKI resistant patients is provided together with a description of the new drugs in clinical or preclinical phases which are developing to overcome resistance.


RESULTS
Future perspective for the 'cure' of CML patients and new drugs designed for this purpose are suggested.


CONCLUSIONS
CML therapy has dramatically changed in the last few years due to the introduction of targeted therapy. Studies on new drugs targeting different pathways other than BCR-ABL are ongoing to improve the clinical results.
Cilloni
Daniela
D
University of Turin, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole 10, 10043, Orbassano Turin, Italy. daniela.cilloni@unito.it
Messa
Emanuela
E
Rotolo
Antonia
A
Saglio
Giuseppe
G
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases