Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies

Ellen Weisberg, Atsushi Nonami, James D. Griffin

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Despite the clinical efficacy achieved with frontline therapies for BCR-ABL-positive disease, such as imatinib and second-generation ABL inhibitors like nilotinib or dasatinib that were originally designed to override insensitivity to imatinib, drug resistance still remains a challenge, especially for patients with advanced-stage chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. The discovery of BCR-ABL point mutations has been a great asset to furthering our understanding of a major cause of drug resistance, as has discovery of multidrug resistance proteins, dysregulation of signaling molecules downstream of BCR-ABL, and insights into the underlying causes of stromal-mediated chemoresistance. Such elucidation of mechanisms of resistance associated with leukemic cell survival is essential for the optimization of current therapies and enhancement of patient survival via delaying or preventing disease recurrence. Here, we present an overview of the use of nilotinib in combination with other agents against BCR-ABL-positive leukemia, as well as solid tumors, for the purpose of increasing clinical efficacy and overriding drug resistance.

Original languageEnglish
Pages (from-to)2233-2242
Number of pages10
JournalArchives of Toxicology
Volume88
Issue number12
DOIs
Publication statusPublished - Nov 29 2014
Externally publishedYes

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Drug Resistance
Leukemia
Pharmaceutical Preparations
P-Glycoproteins
Philadelphia Chromosome
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosomes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Point Mutation
Tumors
Cell Survival
Therapeutics
Cells
Recurrence
Molecules
Survival
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies. / Weisberg, Ellen; Nonami, Atsushi; Griffin, James D.

In: Archives of Toxicology, Vol. 88, No. 12, 29.11.2014, p. 2233-2242.

Research output: Contribution to journalReview article

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