Targeted therapy in chronic lymphocytic leukemia: Past, present, and future

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western world. Recent advances in understanding the biology of B-cell malignancies have resulted in the development of novel agents targeting key prosurvival pathways in the neoplastic B cell. Objective: The goal of this article was to summarize current literature on the emerging therapeutic approaches in CLL and B-cell malignancies. Methods: A literature review was performed, identifyingpathways and key clinical trials involving novel therapies in CLL, with special emphasis on B-cell receptor (BCR)-targeting agents. Results: Understanding the biology of the BCR-signaling pathway has led to identification of novel molecular targets. Most notably, inhibitors of Bruton tyrosine kinase and phosphatidylinositide 3-kinase-δ have entered clinical trials and demonstrated high response rates in CLL, including high-risk disease. Cyclin-dependent kinase inhibitors may evolve into an alternative therapeutic approach in CLL. New drugs that target molecules within and outside of the BCR-signaling pathway have shown promise in preclinical studies. Conclusions: Both preclinical and early clinical trial results involving novel targeted therapies suggest that the standard treatment paradigm in CLL and B-cell malignancies will soon change. Particular attention should be paid to the BCR-targeting agents, whose favorable adverse effect profile may improve the lives of elderly patients with CLL.

Original languageEnglish (US)
Pages (from-to)1258-1270
Number of pages13
JournalClinical therapeutics
Volume35
Issue number9
DOIs
StatePublished - Sep 2013

Keywords

  • B-cell receptor
  • Chronic lymphocytic leukemia
  • Ibrutinib
  • NF-κB

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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