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Targeting ABL and SRC kinases in chronic myeloid leukemia: experience with dasatinib

Alfonso Quintás-Cardama1, Hagop Kantarjian, Jorge Cortes

  • 1The University of Texas, MD Anderson Cancer Center, Department of Leukemia, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030, USA.

Future Oncology (London, England)
|December 13, 2006
PubMed

Insights

Dasatinib effectively treats chronic myeloid leukemia (CML) by inhibiting BCR-ABL kinase, even in cases resistant to imatinib. Further research is exploring its use as a first-line therapy for CML and other blood cancers.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Imatinib resistance in chronic myeloid leukemia (CML) is often caused by ABL kinase domain mutations or SRC family kinase overexpression.
  • Targeting both SRC and ABL kinases with dual inhibitors offers a strategy to overcome imatinib resistance in CML.

Purpose of the Study:

  • To evaluate the efficacy of dasatinib, a dual SRC/ABL kinase inhibitor, in treating chronic myeloid leukemia (CML).
  • To assess dasatinib's activity against imatinib-resistant CML, including various ABL mutant isoforms.

Main Methods:

  • Dasatinib (BMS-354825) was investigated for its inhibitory potency against BCR-ABL and SRC kinases.
  • Clinical efficacy was assessed in Phase I and II studies for patients with CML who had failed imatinib therapy.

Main Results:

  • Dasatinib exhibits approximately 300-fold greater potency against BCR-ABL than imatinib.
  • Dasatinib is effective against all tested ABL mutant isoforms, with the exception of the T315I mutation.
  • Phase I and II studies demonstrated high efficacy of dasatinib in imatinib-refractory CML patients.

Conclusions:

  • Dasatinib is a potent therapeutic agent for CML, particularly in patients resistant to imatinib.
  • Ongoing studies are investigating dasatinib's potential as a front-line treatment for BCR-ABL-expressing hematologic malignancies.

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