Format

Send to

Choose Destination
Genome Med. 2016 Jun 20;8(1):69. doi: 10.1186/s13073-016-0324-x.

Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies.

Author information

1
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia.
2
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia. jerry.shay@utsouthwestern.edu.
3
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA. jerry.shay@utsouthwestern.edu.

Abstract

Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized.

PMID:
27323951
PMCID:
PMC4915101
DOI:
10.1186/s13073-016-0324-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center