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

Abstract:

: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.

journal_name

Adv Exp Med Biol

authors

Taiakina D,Dal Pra A,Bristow RG

doi

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

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

189-204

eissn

0065-2598

issn

2214-8019

journal_volume

772

pub_type

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