Enzastaurin hydrochloride for lymphoma: reassessing the results of clinical trials in light of recent advances in the biology of B-cell malignancies.

Abstract

INTRODUCTION:

The B-cell receptor (BCR) is critical for the development and persistence of B-cell non-Hodgkin lymphoma (B-NHL). Protein kinase C-beta (PKC-?) has been identified as one of the key signaling hubs downstream of the BCR and constitutes a valuable target in B-NHL. As a potent PKC-? inhibitor, enzastaurin is currently being tested in Phase II/III trials.

AREAS COVERED:

This review summarizes the latest results and ongoing clinical trials with enzastaurin in light of basic scientific advances in the understanding of various lymphoid cancers, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) and Waldenstr?m's macroglobulinemia (WM).

EXPERT OPINION:

While its continued clinical development is uncertain, enzastaurin should be regarded as a stepping stone for the development of future therapies; indeed, the recent research has provided valuable insight into the possible molecular mechanisms that explain its limited clinical activity especially in the treatment of DLBCL and MCL. It should be noted that there is still some interest in enzastaurin, in combination, for the treatment of WM.

• Authors: Loic Ysebaert, Franck Morschhauser
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 20 Issue 8 Pg. 1167-74 (Aug 2011) ISSN: 1744-7658 [Electronic] England
• PMID: 21639821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Indoles
• Protein Kinase Inhibitors
• Protein Kinase C
• Protein Kinase C beta
• enzastaurin

Topics

• Animals
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Humans
• Indoles (pharmacology, therapeutic use)
• Lymphoma, B-Cell (drug therapy, enzymology, metabolism)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase C beta
• Protein Kinase Inhibitors (pharmacology, therapeutic use)