Potential Telomere-Related Pharmacological Targets
| Autor: | Kavya Sri Racherla, Joseph Berei, Allison M. Giuffre, Austin D. Anderson, Meet Patel, Monica Saravana Vela, Adam Eckburg, Neelu Puri, Diana Tang, Joshua Dein, Rachel J. Miller, Edward Miliavski, Shreya Deb |
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| Rok vydání: | 2019 |
| Předmět: |
Genome instability
Senescence 0303 health sciences Telomerase DNA damage Cancer Biological Availability Antineoplastic Agents General Medicine Biology Telomere Shelterin medicine.disease 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Neoplasms Drug Discovery Cancer research medicine Humans Telomerase reverse transcriptase 030304 developmental biology |
| Zdroj: | Current topics in medicinal chemistry. 20(6) |
| ISSN: | 1873-4294 |
| Popis: | Telomeres function as protective caps at the terminal portion of chromosomes, containing non-coding nucleotide sequence repeats. As part of their protective function, telomeres preserve genomic integrity and minimize chromosomal exposure, thus limiting DNA damage responses. With continued mitotic divisions in normal cells, telomeres progressively shorten until they reach a threshold at a point where they activate senescence or cell death pathways. However, the presence of the enzyme telomerase can provide functional immortality to the cells that have reached or progressed past senescence. In senescent cells that amass several oncogenic mutations, cancer formation can occur due to genomic instability and the induction of telomerase activity. Telomerase has been found to be expressed in over 85% of human tumors and is labeled as a near-universal marker for cancer. Due to this feature being present in a majority of tumors but absent in most somatic cells, telomerase and telomeres have become promising targets for the development of new and effective anticancer therapeutics. In this review, we evaluate novel anticancer targets in development which aim to alter telomerase or telomere function. Additionally, we analyze the progress that has been made, including preclinical studies and clinical trials, with therapeutics directed at telomere-related targets. Furthermore, we review the potential telomere-related therapeutics that are used in combination therapy with more traditional cancer treatments. Throughout the review, topics related to medicinal chemistry are discussed, including drug bioavailability and delivery, chemical structure-activity relationships of select therapies, and the development of a unique telomere assay to analyze compounds affecting telomere elongation. |
| Databáze: | OpenAIRE |
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