Dasatinib in solid tumors.

Abstract

IMPORTANCE OF THE FIELD:

Dasatinib is an oral, potent adenosine triphosphate-competitive inhibitor of multiple tyrosine kinases including BCR-ABL, c-KIT, platelet-derived growth factor receptor, and Src family kinases (SFKs). It has gained much attention for its use in chronic myeloid leukemia and for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. However, dasatinib is also being explored in solid tumors in ongoing Phase I and II clinical trials.

AREAS COVERED IN THIS REVIEW:

The clinical efficacy of dasatinib in a wide variety of solid tumors and important Phase I/II studies utilizing dasatinib and the optimal dosage used in solid tumors. A literature search was conducted using PubMed/MEDLINE, www.clinicaltrials.gov , and the American Society of Clinical Oncology websites to find relevant Phase I/II clinical trials during 1987-2009.

WHAT THE READER WILL GAIN:

The understanding that the biology and mechanism of Src activation in tumors are not well understood and finding the optimal use of SFK inhibitors in the clinical setting requires further investigation.

TAKE HOME MESSAGE:

In reviewing the clinical safety data of dasatinib in its current use as a Src inhibitor in a wide variety of solid malignancies, dasatinib appears to be safe and is a promising agent for the treatment of metastatic solid tumors refractory to standard therapies.

• Authors: Lori C Kim, Uwe Rix, Eric B Haura
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 19 Issue 3 Pg. 415-25 (Mar 2010) ISSN: 1744-7658 [Electronic] England
• PMID: 20113198 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• src-Family Kinases
• Dasatinib

Topics

• Adult
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Dasatinib
• Humans
• Neoplasm Metastasis
• Neoplasms (drug therapy, physiopathology)
• Protein Kinase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Pyrimidines (adverse effects, pharmacology, therapeutic use)
• Thiazoles (adverse effects, pharmacology, therapeutic use)
• src-Family Kinases (antagonists & inhibitors, metabolism)