The Role of Telomerase in Breast Cancer’s Response to Therapy

Abstract

Currently, breast cancer appears to be the most widespread cancer in the world and the most common cause of cancer deaths. This specific type of cancer affects women in both developed and developing countries. Prevention and early diagnosis are very important factors for good prognosis. A characteristic feature of cancer cells is the ability of unlimited cell division, which makes them immortal. Telomeres, which are shortened with each cell division in normal cells, are rebuilt in cancer cells by the enzyme telomerase, which is expressed in more than 85% of cancers (up to 100% of adenocarcinomas, including breast cancer). Telomerase may have different functions that are related to telomeres or unrelated. It has been shown that high activity of the enzyme in cancer cells is associated with poor cell sensitivity to therapies. Therefore, telomerase has become a potential target for cancer therapies. The low efficacy of therapies has resulted in the search for new combined and more effective therapeutic methods, including the involvement of telomerase inhibitors and telomerase-targeted immunotherapy.

All-trans-retinoic acid modulates glycolysis via H19 and telomerase: the role of mir-let-7a in estrogen receptor-positive breast cancer cells

“…Having a better characterization of the known and newly discovered potential markers would be of importance for the care and treatment of breast cancer [ 43 ]. LncRNAs particularly H19 [ 44 , 45 ] and hTERT [ 16 ] are important biomarkers in breast cancer based on their main roles in glycolysis [ 46 , 47 ]. Indeed, retinoic acid has inhibitory effects on proliferation and cancer cell migration by targeting cell proliferation proteins, such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) [ 41 ].…”

“…Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for BC treatment [ 14 ]. Increased telomerase activity is observed in most malignant tumors [ 15 ]; therefore, different therapeutic approaches for telomerase, mainly specific inhibitors, have been developed to reduce tumorigenicity in BC [ 16 ]. Additionally, lncRNAs are involved in transcription, translational regulation, and cell development.…”

Generation and application of immortalized sheep fetal fibroblast cell line

“…Various immortalization genes have been identified, with human telomerase reverse transcriptase (HTERT) and SV40T antigen being the most extensively studied. HTERT activates telomerase to prevent telomere shortening and achieve cell immortality [19], whereas SV40T antigen inhibits Rb through P53, preventing cell aging and apoptosis by promoting cell immortalization [20]. The SV40T antigen triggers the Rb protein inactivation (pRB, p130, and p107) and thereby activates E2Fdependent transcription, an increase in the S-phase ratio, cell proliferation, and, ultimately, immortality [21].…”

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

“…In addition to regulating telomere length (canonical function), telomerase and hTERT perform many other functions such as impact on proliferation (due to Wnt/β-catenin pathway or NF-kB and p65 pathway), cell survival, apoptotic resistance, adhesion, migration, stem cell renewal, inflammation, chromatin configuration and DNA repair, mitochondrial DNA protection and resistance to ionizing radiation (non-canonical functions) [209,210]. Thus, telomerase and hTERT were identified as potential therapeutic targets for cancer treatment [211].…”