Telomere and Telomerase as Targets for Cancer Therapy

Abstract

Telomere maintenance and telomerase reactivation is essential for the transformation of most human cancer cells. Telomere shortening to the threshold length, mutations of the telomere-associated proteins, and/or telomerase RNA lead to telomeric dysfunction and therefore genomic instability. Telomerase up-regulation in 85% of human cancer cells has become a hallmark of cancers, hence a promising target for anticancer therapy. In this review, we discuss the mechanism of cancer due to telomere dysfunction and the resulting biological effects, the control of telomerase activity, and the new developments in cancer therapies targeting telomere and telomerase.

Inhibition of telomerase activity and cell growth by free and nanoliposomal forms of punicalagin in human leukemia cell line K562

“…In cancer therapy research, many different synthetic chemical agents have been proposed for telomerase inhibition but most of these compounds have severe toxic side effects on normal cells [5]. As a result, extensive studies have been carried out in search of compounds that are capable of inhibiting telomerase activity and retarding growth of cancer cells without affecting normal cells [6,7].…”

Targeting the Telomere with T-Oligo, G Quadruplex Stabilizers, and Tankyrase Inhibitors

“…It is comprised of two major components, an RNA template complementary to the 3' overhang that acts as a primer, called hTR, and a human ribonucleoprotein reverse transcriptase, hTERT, that catalytically adds nucleotides to the 3' overhang [7,8]. Telomerase has recently become an attractive target for cancer therapies because it is inappropriately overexpressed in more than 85% of cancers, while most normal cells have minimal or no detectable activity [9,10].…”

Early Growth Response Protein-1 Promoter-Mediated Synergistic Antitumor Effect of hTERTC27 Gene Therapy and 5-Flurorouracil on Nasopharyngeal Carcinoma

“…4,5 Telomerase is an attractive target for cancer gene therapy, because it is highly active in most cancer cells, but it is inactive in most somatic cells. 6 The primary function of telomerase is to maintain the telomere length and to prolong the life span of cells. 7 The dysfunction of telomerase will prevent the long-term survival of tumor cells and lead to cell death or senescence.…”

“…6,[22][23][24] We have newly constructed the hTERTC27 polypeptide and previously reported that this polypeptide rendered the HeLa cells more sensitive to H 2 O 2 treatment. Moreover, our previous study showed that overexpressed hTERTC27 induced telomere dysfunction in HeLa cells and inhibits cervical carcinoma and glioblastoma tumor growth and tumorigenicity.…”