Telomeres and telomerase in prostate cancer development and therapy

Mindy Kim Graham, Alan Keith Meeker

Research output: Contribution to journalReview article

Abstract

Aberrations in telomere biology are among the earliest events in prostate cancer tumorigenesis and continue during tumour progression. Substantial telomere shortening occurs in prostate cancer cells and high-grade prostatic intraepithelial neoplasia. Not all mechanisms of telomere shortening are understood, but oxidative stress from local inflammation might accelerate prostatic telomere loss. Critically short telomeres can drive the accumulation of tumour-promoting genomic alterations; however, continued telomere erosion is unsustainable and must be mitigated to ensure cancer cell survival and unlimited replication potential. Prostate cancers predominantly maintain telomeres by activating telomerase, but alternative mechanisms of telomere extension can occur in metastatic disease. Telomerase activity and telomere length assessment might be useful in prostate cancer diagnosis and prognosis. Telomere shortening in normal stromal cells has been associated with prostate cancer, whereas variable telomere lengths in prostate cancer cells and telomere shortening in cancer-associated stromal cells correlated with lethal disease. Single-agent telomerase-targeted treatments for solid cancers were ineffective in clinical trials but have not been investigated in prostate cancer and might be useful in combination with established regimens. Telomere-directed strategies have not been explored as extensively. Telomere deprotection strategies have the advantage of being effective in both telomerase-dependent and telomerase-independent cancers. Disruption of androgen receptor function in prostate cancer cells results in telomere dysfunction, indicating telomeres and telomerase as potential therapeutic targets in prostate cancer.

Original languageEnglish (US)
Pages (from-to)607-619
Number of pages13
JournalNature Reviews Urology
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2017

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Telomerase
Telomere
Prostatic Neoplasms
Telomere Shortening
Therapeutics
Neoplasms
Stromal Cells
Prostatic Intraepithelial Neoplasia
Androgen Receptors
Cell Survival
Carcinogenesis
Oxidative Stress
Clinical Trials

ASJC Scopus subject areas

  • Urology

Cite this

Telomeres and telomerase in prostate cancer development and therapy. / Graham, Mindy Kim; Meeker, Alan Keith.

In: Nature Reviews Urology, Vol. 14, No. 10, 01.10.2017, p. 607-619.

Research output: Contribution to journalReview article

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