Journal article
Potential Telomere-Related Pharmacological Targets
Current topics in medicinal chemistry, Vol.20(6), pp.458-484
01/01/2020
DOI: 10.2174/1568026620666200109114339
PMID: 31916516
Abstract
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.
Details
- Title: Subtitle
- Potential Telomere-Related Pharmacological Targets
- Creators
- Joseph Berei - University of Illinois Chicago, Rockford campusAdam Eckburg - University of Illinois Chicago, Rockford campusEdward Miliavski - University of Illinois Chicago, Rockford campusAustin D. Anderson - University of Illinois Chicago, Rockford campusRachel J. Miller - University of Illinois Chicago, Rockford campusJoshua Dein - University of Illinois Chicago, Rockford campusAllison M. Giuffre - University of Illinois Chicago, Rockford campusDiana Tang - University of Illinois Chicago, Rockford campusShreya Deb - University of Illinois Chicago, Rockford campusKavya Sri Racherla - University of Illinois Chicago, Rockford campusMeet Patel - University of Illinois Chicago, Rockford campusMonica Saravana Vela - University of Illinois Chicago, Rockford campusNeelu Puri - University of Illinois Chicago, Rockford campus
- Resource Type
- Journal article
- Publication Details
- Current topics in medicinal chemistry, Vol.20(6), pp.458-484
- DOI
- 10.2174/1568026620666200109114339
- PMID
- 31916516
- NLM abbreviation
- Curr Top Med Chem
- ISSN
- 1568-0266
- eISSN
- 1873-5294
- Publisher
- Bentham Science Publ Ltd
- Number of pages
- 27
- Language
- English
- Date published
- 01/01/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985218624702771
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