Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer

Taiakina, Daria; Dal Pra, Alan; Bristow, Robert G (2014). Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer. In: Koumenis, Constantinos; Hammond, Ester; Giaccia, Amato (eds.) Tumor Microenvironment and Cellular Stress. Advances in Experimental Medicine and Biology: Vol. 772 (pp. 189-204). New York: Springer 10.1007/978-1-4614-5915-6_9

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Intratumoral hypoxia is prevalent in many solid tumors and is a marker of poor clinical prognosis in prostate cancer. The presence of hypoxia is associated with increased chromosomal instability, gene amplification, downregulation of DNA damage repair pathways, and altered sensitivity to agents that damage DNA. These genomic changes could also lead to oncogene activation or tumor suppressor gene inactivation during prostate cancer progression. We review here the concept of repair-deficient hypoxic tumor cells that can adapt to low oxygen levels and acquire an aggressive "unstable mutator" phenotype. We speculate that hypoxia-induced genomic instability may also be a consequence of aberrant mitotic function in hypoxic cells, which leads to increased chromosomal instability and aneuploidy. Because both hypoxia and aneuploidy are prognostic factors in prostate cancer, a greater understanding of these biological states in prostate cancer may lead to novel prognostic and predictive tests and drive new therapeutic strategies in the context of personalized cancer medicine.

Item Type:

Book Section (Book Chapter)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology

UniBE Contributor:

Dal Pra, Alan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0065-2598

ISBN:

978-1-4614-5914-9

Series:

Advances in Experimental Medicine and Biology

Publisher:

Springer

Language:

English

Submitter:

Beatrice Scheidegger

Date Deposited:

16 Mar 2015 14:15

Last Modified:

09 Nov 2015 10:04

Publisher DOI:

10.1007/978-1-4614-5915-6_9

PubMed ID:

24272360

BORIS DOI:

10.7892/boris.64654

URI:

https://boris.unibe.ch/id/eprint/64654

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