The current knowledge on telomerase and telomeres indicates that these enzymes have significant roles in human aging, cellular senescence, and cell proliferation. Telomeres refer to unique structures located at the end of eukaryotic chromosomes that serve to maintain chromosome stability and minimize the chances of enzymatic end-degradation. In addition to these roles, telomeres also play a key function in the process of cell replication and orientation of the cellular nucleus by providing a platform upon which the nuclear matrix is attached. In most cases, human cancer compels the activation of telomerase in the form of a hallmark with an objective of permitting limitless tumor cells proliferation. As such, the significance of telomerase in fostering cancer growth cannot be underestimated. Telomerase/telomeres enzymes inhibition is the next frontier in cancer therapy.
Telomeres and Cancer Development
Cancer development is enhanced by aberrations in telomere maintenance and telomere length. Telomeres are composed of nucleotides that act as the caps of linear DNA. Since these enzymes lack the capacity to encode proteins, they fail to qualify as genes (Basu et al., 2013). Owing to the fact that telomere overhang during the process of cell division, the repetitive tags of these enzymes located at the ends of linear chromosomes tends to decrease in length as the process of DNA replication continues. In this view, the decrease in length of telomere enzymes especially in healthy cells results in regulated apoptosis and thus, acting as an approach of removing DNA that may be susceptible to altered expression or mutation (Graham & Meeker, 2017).
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"Telomerase/Telomeres in the Field of Biology".
De Jesus and Blasco (2013) argue that clearance of DNA liable to altered expression can result in cancer, infection, and other types of diseases. The validity of this argument can be affirmed by the fact that telomerase activation is often perceived as an early process in cancer initiation. Telomerase in cancer is activated by varied oncogenes such as Wnt and Myc, which serves to regulate the transcriptional process of telomerase (Heaphy et al., 2013). Besides the canonical significance of telomerase in ensuring that the length of telomeres remains above the acceptable length, studies have shown that telomerase has a capacity to impact pathways such as metabolism and Wnt targets, which have an impact on cancer growth.
Telomeres Enzymes and Cancer Therapy
With advances in technology and knowledge in the healthcare sector, the approaches used in cancer treatment has undergone numerous changes with a goal of increasing precision, effectiveness, and chances of survival. Most of the approaches used to treat cancer are based on the fact that normal human cells have limited capacity to proliferate as opposed to cells obtained from tumors, which have an infinite growth potential. Telomere shortening comes after normal proliferation and has a significant impact on cellular mortality (Basu et al., 2013). In this perspective, regulating the factors that determine the length of telomere enzymes will go a long way in managing cancer prevalence.
Researchers have proposed varied options that can be used in the up-regulation of the length of telomerase, which plays a significant role in influencing the mortality of abnormal human cells. The vast of studies have paid close attention to phosphorylation-stirred boost in Telomerase Reverse Transcriptase (TERT) activity and the control of TERT expression. According to Graham and Meeker (2017), both approaches are effective especially in addressing liver, GI tract, and prostate cancer. Some of the elements that act as co-regulators and active transcription factors include MYC oncogene, Menin, and WT1. Reddel (2014) notes that TERT transcriptional activities are also enhanced through mutation, especially when it occurs within the primary region of TERT. Such processes result in the creation of de novo uniting motifs, which are compatible with ETS elements that enhances transcription. Bladder carcinomas, liposarcomas, melanomas, gliomas, hepatocellular are some of the areas where chances of TERT promoter mutations occurring are high. Heaphy et al (2013) allude that TERT promoter mutation has found use in monitoring and detection of bladder cancer through the use of a urinary biomarker.
Maintaining Telomeres and Cancer Therapy
Effective telomere maintenance provides the best approach to developing cancer therapies. According to Reddel (2014), the most common intervention of telomere maintenance involves regulating the catalytic events that occur during the synthesis of telomeric DNA by the ALT or telomerase. Inhibitors are often used in the regulation of catalytic events with a goal of interfering with processes such as substrate binding, enzyme translocation, and transcription of telomeric DNA, which are involved in the lengthening of telomerase enzymes (Basu et al., 2013). Inhibiting this process serves to ensure that telomerase catalyzed reaction does not occur and ultimately, the lengthening of telomerase enzyme is managed. Graham and Meeker (2017) argue that mediated lengthening of telomerase can also be significantly inhibited by focusing on other steps that form part of these enzyme lengthening process. As such, the assembly of telomerase enzymes and their subunits can be converted into complex active enzymes through modulated splicing approach. De Jesus and Blasco (2013) affirm that such splicing results in the formation of proteins that are catalytically inactive in case they undergone any translation process. In this perspective, management of splicing can be adopted as an intervention of addressing cancer.
In conclusion, cancer therapy approaches continue to advance owing to the need to design approaches that are more effective, safe and precise. Telomerase/telomeres enzymes inhibition through the regulation of catalytic events that occurs during the synthesis of telomeric NDA is an effective cancer therapy strategy under development. The up-regulation of the length of telomerase and management of splicing of telomerase enzyme can also be used as a therapeutic approach to cancer.
- Basu, N., Skinner, H. G., Litzelman, K., Vanderboom, R., Baichoo, E., & Boardman, L. A. (2013). Telomeres and telomere dynamics: relevance to cancers of the GI tract. Expert review of Gastroenterology & Hepatology, 7(8), 733-748. 1
- De Jesus, B. B., & Blasco, M. A. (2013). Telomerase at the intersection of cancer and aging. Trends in genetics, 29(9), 513-520.
- Graham, M. K., & Meeker, A. (2017). Telomeres and telomerase in prostate cancer development and therapy. Nature Reviews Urology, 14(10), 607-619.
- Heaphy, C. M., Yoon, G. S., Peskoe, S. B., Joshu, C. E., Lee, T. K., Giovannucci, E., … & De Marzo, A. M. (2013). Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer discovery, 3(10), 1130-1141.
- Reddel, R. (2014). Telomere maintenance mechanisms in cancer: clinical implications. Current pharmaceutical design, 20(41), 6361-6374.
