Tumor Cell Hypoxia and the Hypoxia-Response Signaling System as a Target for Prostate Cancer Therapy

Aristotelis   G.   Anastasiadis; Debra   L.   Bemis; Brian   C.   Stisser; Laurent      Salomon; Mohamed   A.   Ghafar; Ralph      Buttyan

doi:10.2174/1389450033491136

Abstract

The accumulation of cancerous cells within a growing prostate tumor can deprive them of adequate vascular support. Without this support, the affected tumor cells become hypoxic, a condition that is usually unfavorable for the further growth and survival of eukaryotic cells. Mammalian cells, however, have the ability of responding to a hypoxic environment by activating a “hypoxia-response” signaling system. Ultimately, this signaling system upregulates the expression of a network of gene products that increase the propensity of the cell to survive even in this adverse environment. With increasing evidence that hypoxia and an activated hypoxia-response signaling system can influence progression (via increased angiogenic propensity and apoptotic resistance) and the therapeutic responsiveness of prostate cancer cells, this review will examine the concept of targeting hypoxia or the hypoxia-response system of prostate tumor cells as a means to suppress prostate tumor progression and metastasis or perhaps even as a means for eliminating prostate tumors in advanced prostate cancer patients

Keywords: prostate cancer, hypoxia, Hypoxia Inducible Factor, angiogenesis, vegf, apoptosis, akt/protein kinase b