Integrating the DNA damage and protein stress responses during cancer development and treatment.

Abstract

Cells have developed during evolution a wide spectrum of stress response modules to assure homeostasis. The genome and proteome damage response pathways constitute the pillars of this interwoven "defensive" network. Consequently, the deregulation of these pathways correlates with aging and various pathophysiological states, including cancer. In the present review we highlight: i) the structure of the genome and proteome damage response pathways, ii) their functional crosstalk and, iii) the conditions under which they predispose to cancer. Within this context, we emphasize the role of oncogene-induced DNA damage as a driving force that shapes the cellular landscape for the emergence of the various hallmarks of cancer. We also discuss potential means to exploit key cancer-related alterations of the genome and proteome damage response pathways in order to develop novel efficient therapeutic modalities. This article is protected by copyright. All rights reserved.