Current Pharmaceutical Design - Volume 20, Issue 41, 2014

The discovery of new cancer-related targets and the development of innovative therapeutic interventions are mainly based on the identification of genes involved in pathways selectively deregulated in cancer cells. The unlimited replicative potential is one of the principal hallmarks of cancer and it requires the activation of telomere maintenance mechanisms (TMMs). Two TMMs are currently known in human cancer, namely t Read More

The presence of immortal cell populations with an up-regulated telomere maintenance mechanism (TMM) is an almost universal characteristic of cancers, whereas normal somatic cells are unable to prevent proliferation-associated telomere shortening and have a limited proliferative potential. TMMs and related aspects of telomere structure and function therefore appear to be ideal targets for the development of anti Read More

Most cancer genomes show abnormalities in chromosome structure and number, two types of aberrations that could share a common mechanistic origin through proliferation-dependent loss of telomere function. Impairment of checkpoints that limit cell proliferation when telomeres are critically short might allow unrestrained cell division. The resulting uncapped chromosomes can fuse to each other, forming unstable co Read More

Telomerase activity is essential for human cancer cells in order to maintain telomeres and provide unlimited proliferation potential and cellular immortality. However, additional non-telomeric roles emerge for the telomerase protein TERT that can impact tumourigenesis and cancer cell properties. This review summarises our current knowledge of non-telomeric functions of telomerase in human cells, with a special emph Read More

The activation of telomere maintenance mechanisms, which rely on telomerase reactivation or on a recombination-based process known as alternative lengthening of telomeres, guarantees a limitless proliferative potential to human tumor cells. To date, the molecular underpinnings that drive the activation of telomere maintenance mechanisms during tumorigenesis are poorly understood, but there are indications that co Read More

Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity. Telo Read More

Telomerase is a specialized enzymatic complex responsible for the synthesis of telomeric repeats 5'-TTAGGG-3' localized at the ends of eukaryotic chromosomes. This mechanism prevents shortening of telomeres after each cell division. The enzyme is detected in about 85% of human tumors, but it is not expressed in normal cells or its expression is significantly lower. Consequently, it provides the cancer cells immortality. Thus, Read More

The telomere-telomerase system has a unique role in the biology of cancer. Telomere maintenance, mostly affected by the up regulation of telomerase activity, is a prerequisite for perpetuation of malignant cells. This fundamental biologic feature defines telomere maintenance as an attractive therapeutic target for most types of cancer. This review summarizes some critical aspects of telomere biology with special e Read More

Telomeres are essential for cell proliferation and tumor cell immortalization requires the presence of a telomere maintenance mechanism. Thus, interfering with this mechanism constitutes a potential means to impede cell proliferation and tumor progression. Many cancer cells rely on telomerase activity to ensure indefinite proliferation capacity and developing therapeutic approaches that target telomerase has attract Read More

Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in various cellular fu Read More

The discovery of novel nucleic acid folding architectures bears a twofold interest related to the structural properties of unprecedented forms and to their functional significance. In addition, physiologically and pathologically important processes can be impaired by endogenous or xenobiotic ligands interacting with specific target sequences. In this paper we will focus on recent advances in the study of telomeric G-quadruplex Read More