TY - JOUR
T1 - Telomere maintenance and tumorigenesis
T2 - An "ALT"ernative road
AU - Stewart, Sheila A.
PY - 2005/3
Y1 - 2005/3
N2 - The acquisition of cellular immortality is a critical step in human tumorigenesis. While the vast majority of human tumors activate the catalytic component of telomerase (hTERT) to stabilize their telomeres and attain immortality, a significant portion (7-10%) utilize a poorly defined alternative form of telomere maintenance referred to as ALT. Interestingly, telomerase activation is often favored in tumors arising from the epithelial compartment whereas ALT occurs in a more significant portion of tumors that arise from tissues of mesenchymal origin. This observation raises the possibility that cell type specific mechanisms favor the activation of telomerase versus ALT in human tumorigenesis. Because cellular immortality is critical to tumorigenesis it may represent an important anti-neoplastic target. Indeed, several approaches have successfully eliminated telomerase activity in human tumor models and some of these approaches are now moving into clinical trials. While these results are encouraging, it is clear that these approaches will have no impact on cells that utilize the ALT mechanism for telomere maintenance. Furthermore, the existence of ALT raises the possibility that telomerase-positive tumors undergoing anti-telomerase therapies may escape by activating the ALT pathway. For these reasons a detailed understanding of the ALT pathway is critical to the future design of anti-neoplastic therapies.
AB - The acquisition of cellular immortality is a critical step in human tumorigenesis. While the vast majority of human tumors activate the catalytic component of telomerase (hTERT) to stabilize their telomeres and attain immortality, a significant portion (7-10%) utilize a poorly defined alternative form of telomere maintenance referred to as ALT. Interestingly, telomerase activation is often favored in tumors arising from the epithelial compartment whereas ALT occurs in a more significant portion of tumors that arise from tissues of mesenchymal origin. This observation raises the possibility that cell type specific mechanisms favor the activation of telomerase versus ALT in human tumorigenesis. Because cellular immortality is critical to tumorigenesis it may represent an important anti-neoplastic target. Indeed, several approaches have successfully eliminated telomerase activity in human tumor models and some of these approaches are now moving into clinical trials. While these results are encouraging, it is clear that these approaches will have no impact on cells that utilize the ALT mechanism for telomere maintenance. Furthermore, the existence of ALT raises the possibility that telomerase-positive tumors undergoing anti-telomerase therapies may escape by activating the ALT pathway. For these reasons a detailed understanding of the ALT pathway is critical to the future design of anti-neoplastic therapies.
UR - http://www.scopus.com/inward/record.url?scp=18044370239&partnerID=8YFLogxK
U2 - 10.2174/1566524053586653
DO - 10.2174/1566524053586653
M3 - Review article
C2 - 15974880
AN - SCOPUS:18044370239
SN - 1566-5240
VL - 5
SP - 253
EP - 257
JO - Current Molecular Medicine
JF - Current Molecular Medicine
IS - 2
ER -