RT Journal Article SR Electronic T1 Tumor Cell-protective Catalase as a Novel Target for Rational Therapeutic Approaches Based on Specific Intercellular ROS Signaling JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2599 OP 2624 VO 32 IS 7 A1 GEORG BAUER YR 2012 UL http://ar.iiarjournals.org/content/32/7/2599.abstract AB Reactive oxygen species (ROS) exhibit procarcinogenic effects at multiple stages during multistep oncogenesis. As a hallmark of the transformed state, extracellular superoxide anions generated by NADPH oxidase1 (NOX1) are centrally involved in the control of the transformed state. These pro-carcinogenic effects of ROS are counterbalanced by specific ROS-dependent apoptosis induction in malignant cells, based on four interconnected signaling pathways. Tumor progression selects for a phenotype characterized by resistance to ROS-dependent apoptotic signaling. Resistance is based on membrane-associated catalase in tumor cells, which therefore represents a promising and unique target for specific tumor therapy. Novel approache, developed in vitro, utilize antibody-mediated inhibition of catalase or ROS-driven singlet oxygen generation and subsequent inactivation of tumor cell catalase as initial steps. As a consecutive step, malignant cell-generated superoxide anions then drive apoptotic signaling with high selectivity for malignant cells. We propose to translate this complex but well-established ROS-dependent signaling chemistry into novel approaches for experimental therapy in vivo.