Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 20, Issue 6, Pages 410-432Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568026620666200106145340
Keywords
Cancer therapy; Gene transcription; TERC; TERRA; TERT; TERT promoter mutation; Telomerase; Telomere
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Funding
- China Postdoctoral Science Foundation [2019M652404]
- Swedish Cancer Society [19 0018 Pj]
- Swedish Research Council [2018-02993]
- Cancer Society in Stockholm [171223]
- Karolinska Institutet Foundation [2018-01524]
- Swedish Foundation for International Cooperation in Research and Higher Education (STINT) [CH2016-6632]
- Ruth and Richard Julin Foundation
- Nanna Svartz Foundation [201800183]
- Swedish Research Council [2018-02993] Funding Source: Swedish Research Council
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Telomeres are structurally nucleoprotein complexes at termini of linear chromosomes and essential to chromosome stability/integrity. In normal human cells, telomere length erodes progressively with each round of cell divisions, which serves as an important barrier to uncontrolled proliferation and malignant transformation. In sharp contrast, telomere maintenance is a key feature of human malignant cells and required for their infinite proliferation and maintenance of other cancer hallmarks as well. Thus, a telomere-based anti-cancer strategy has long been suggested. However, clinically efficient and specific drugs targeting cancer telomere-maintenance have still been in their infancy thus far. To achieve this goal, it is highly necessary to elucidate how exactly cancer cells maintain functional telomeres. In the last two decades, numerous studies have provided profound mechanistic insights, and the identified mechanisms include the aberrant activation of telomerase or the alternative lengthening of DOI: telomere pathway responsible for telomere elongation, dysregulation and mutation of telomere-associated factors, and other telomere homeostasis-related signaling nodes. In the present review, these various strategies employed by malignant cells to regulate their telomere length, structure and function have been summarized, and potential implications of these findings in the rational development of telomere-based cancer therapy and other clinical applications for precision oncology have been discussed.
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