Telomerase in hematologic malignancies.

Abstract

PURPOSE OF REVIEW:

The activation of telomere maintenance pathways has long been regarded as a key hallmark of cancer and this has propelled the development of novel inhibitors of telomerase. In this review, we detail the background biology on telomere maintenance in health and disease, then concentrate on the recent preclinical and clinical development behind targeting telomerase in blood cancers.

RECENT FINDINGS:

Preclinical and clinical studies have shown that imetelstat, a competitive inhibitor of telomerase, has activity in certain hematologic malignancies, in particular the myeloproliferative neoplasms and acute myeloid leukemia.

SUMMARY:

Telomerase inhibition has shown remarkable efficacy in myeloid malignancies, and current and future preclinical and clinical studies are necessary to comprehensively investigate its underlying mechanism of action. Future work should identify the potential genetic susceptibilities to telomerase inhibition therapy, and evaluate rational combinations of telomerase inhibitors with chemotherapy and other novel agents. Robust preclinical evaluation is essential to best translate these new agents successfully into our clinical treatment algorithm for myeloid and other blood cancers.

• Authors: Claudia Bruedigam, Steven W Lane
• Journal: Current opinion in hematology (Curr Opin Hematol) Vol. 23 Issue 4 Pg. 346-53 (07 2016) ISSN: 1531-7048 [Electronic] United States
• PMID: 27213497 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)

Chemical References

• Telomerase

Topics

• Animals
• Clinical Studies as Topic
• Drug Evaluation, Preclinical
• Enzyme Activation
• Gene Expression Regulation
• Hematologic Neoplasms (drug therapy, etiology, metabolism, pathology)
• Humans
• Molecular Targeted Therapy
• Mutation
• Telomerase (antagonists & inhibitors, genetics, metabolism)
• Telomere (genetics, metabolism)
• Telomere Homeostasis
• Treatment Outcome