Telomerase presents over-expression in most of cancer cells and has been a near-universal marker of cancer. Studies revealed that inhibiting telomerase activity by utilizing oligonucleotides to down-regulate the expression of intracellular human telomerase reverse transcriptase (hTERT) mRNA was an effective method to achieve anti-tumor therapy. Considering oncogenic microRNA-21 has been proved to indirectly up-regulate hTERT expression and drive cancer metastasis and aggression through increased telomerase activity, here we constructed a AS1411-functionallized oligonucleotide-conjugated gold nanoprobe (Au-nanoprobe) to simultaneously down-regulate intracellular microRNA-21 and hTERT mRNA by using anti-sense oligonucleotide technology to explore their targeted anti-tumor therapy effect. In vitro cell studies demonstrated that Au-nanoprobes could effectively induce apoptosis and inhibit the proliferation of cancer cells through down-regulating intracellular hTERT activity. In vivo imaging and anti-tumor studies revealed that Au-nanoprobes could accumulate at the tumor site and inhibit the growth of MCF-7 tumor xenografted on balb/c nude mice, thus exert the potential of anti-tumor therapy.

Telomerase is an enzyme which is culpable for the aliment and stability of telomeres. It also maintains the genomic integrity and chromosomal stability. The progressive shortening of telomeres may cause chromosomal instability and alternation in the telomerase. It may cause telomere attrition which can lead to oncogenic incidence in human. Cancer is a disease which is induced by genetic alternations in genes. The genetic mutation within the hTERT is a common type of scenario which is generally found above 90 percent of cancer. In cancer, the length of telomere and the activity of telomerase are very important for cancer cells to proliferate and also for the survival of tumors. Cancer cells regulate through several pathways to increase telomerase activity. There have been several advancements developed to inhibit the telomerase activity in cancer cell but the repercussion of those has demonstrated many adverse effects. Research on AAVs mediated telomerase gene therapy has demonstrated prominent outcomes in animal trials. Thus, it has the potential to bring significance shine in the telomerase cancer therapeutics. Here, in this review article we have analyzed studies related to telomerase gene therapeutics to cure cancer. We also have summarized the telomerase function and mechanism of action to cause cancer. Moreover, other current development in the clinical advances of telomerase inhibition in cancer is described.

Background/Objectives: Malignant neoplasms represent the most common diseases worldwide, and breast cancer is the most commonly diagnosed cancer type in the female population. One of the critical features of this cancer type is the ability to metastasize. This process is related to adhesion, migration, and invasiveness. As demonstrated, the catalytic telomerase subunit, hTERT, may control these processes. The expression and activity of telomerase in normal somatic cells are very low or absent, which makes it a universal and attractive target for cancer diagnostics and therapy; Methods: In this work, we assessed the influence of telomerase inhibitors TMPyP4, BIBR 1532, or imetelstat on the ability to form spheroids in MCF7 and MDA-MB-231 breast cancer cells. Cells of both lines were treated with specific compounds in concentrations: TMPyP4 - 5, 10, 20 µM; BIBR 1532 - 1, 5, 10 µM or imetelstat 1, 5, 10 µM for 72 hours. Cells were then trypsinized and applied to 96-well low-adhesive plates at 500 cells per well, followed by observation at different time intervals, i.e., 24, 48, and 72 hours; Results: As shown, the applied telomerase inhibitors influenced the ability of MCF7 and MDA-MB-231 breast cancer cells to form spheroids in a concentration- and incubation-time-dependent manner; Conclusions: Although the mechanism of this phenomenon has not been fully understood, it seems that the use of telomerase expression/activity inhibitors to reduce the adhesive capacity and metastatic potential of breast cancer cells may play a significant role in cancer therapy.

Tumor invasion, metastasis, and recrudesce remain a considerable challenge in the treatment of gastric cancer (GC). Herein, we first identified that RBFOX3 (RNA binding protein fox-1 homolog 3) was significantly up-regulated in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro as well as in vivo. Furthermore, RBFOX3 increased cell invasion and migration ability. Interestingly, both the suppression of GC cell multiplication and invasion moderated by the silencing of RBFOX3 was rescued by HTERT up-regulation. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil (5-Fu) by repressing RBFOX3. Mechanistically, exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression thereby enhancing the division and development of GC cells. Importantly, our findings revealed that RBFOX3 interacted with AP-2β to modulate the HTERT expression as demonstrated by co-immunoprecipitation analysis. In conclusion, our study indicates that high expression of RBFOX3 promotes GC progression and development but predicts worse prognosis by stimulating HTERT signaling. Moreover, the results suggest that the RBFOX3/AP-2β/HTERT pathway is a novel target for the development of therapeutic agents for the prevention and treatment of GC reappearance and metastasis.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.