Overcoming drug resistance in chronic myeloid leukemia.
OBJECTIVE
Despite the excellent clinical results with imatinib in chronic myeloid leukemia, most patients have minimal residual disease and others will develop resistance and may eventually progress. Thus there is a need for developing approaches to overcome and prevent resistance to imatinib.


RESULTS
Several new agents have been developed with significant activity in imatinib-resistant chronic myeloid leukemia. A second generation of more potent tyrosine kinase inhibitors, some with dual activity against Abl and Src, have shown very impressive results. Other agents, such as hypomethylating agents, farnesyl transferase inhibitors and homoharringtonine, have also shown preclinical and clinical promise. The use of vaccines as a way of providing an immunomodulatory approach to chronic myeloid leukemia is starting to develop as a major strategy to achieve eradication of the disease.


CONCLUSIONS
Multiple effective agents are being developed to overcome resistance to imatinib. The challenge for the future is to incorporate them into effective strategies that can eliminate the disease and cure all patients with chronic myeloid leukemia.
Cortes
Jorge
J
Department of Leukemia, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jcortes@mdanderson.org
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019496:Cancer Vaccines; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D023421:Models, Animal; D018365:Neoplasm, Residual; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001549:Benzamides; D019496:Cancer Vaccines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D051231:Farnesyltranstransferase; D019061:src-Family Kinases