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Center of Excellence In Genomic Medicine Research
Document Details
Document Type
:
Article In Journal
Document Title
:
Cancer and telomeres—an ALTernative to telomerase
Cancer and telomeres—an ALTernative to telomerase
Document Language
:
English
Abstract
:
To grow indefinitely, human cancer cells must counteract the progressive loss of telomeric DNA that universally accompanies cell division. To do this, about 85 to 90% of cancers use telomerase (1–3), an enzyme that synthesizes the tandem 5′-TTAGGG-3′ hexanucleotide repeats of telomeric DNA by reverse transcription using its own RNA subunit as a template. Because telomerase is not expressed in most normal human cells, telomerase inhibition is considered an almost universal oncology target, and several clinical trials are under way (4). However, the future success of inhibiting telomerase to treat cancer is far from assured. Indeed, ∼10 to 15% of human cancers lack detectable telomerase activity (3), and many of these use an alternative lengthening of telomeres (ALT) mechanism (5). These ALT-expressing tumors would not be expected to respond to anti-telomerase therapies, and telomerase-expressing tumors could become resistant by switching to an ALT mechanism, as has recently been shown in mice (6). Here we present a brief history of ALT research, outline what is left to learn about the pathway, and propose it as a valuable drug target both alone and in combination with telomerase as a dual-targeted anticancer strategy.
ISSN
:
0036-8075
Journal Name
:
Science
Volume
:
336
Issue Number
:
6087
Publishing Year
:
1433 AH
2012 AD
Article Type
:
Article
Added Date
:
Tuesday, March 8, 2016
Researchers
Researcher Name (Arabic)
Researcher Name (English)
Researcher Type
Dr Grade
Email
Jerry W Shay
Shay, Jerry W
Investigator
jerry.shay@utsouthwestern.edu
Roger R Reddel
Reddel, Roger R
Researcher
Woodring E Wright
Wright, Woodring E
Researcher
Files
File Name
Type
Description
38438.pdf
pdf
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