Oxidative Stress in Tumor Angiogenesis - Therapeutic Targets

Title: Oxidative Stress in Tumor Angiogenesis - Therapeutic Targets

Volume: 16 Issue: 35

Author(s): Magdalena Tertil, Alicja Jozkowicz and Jozef Dulak

Affiliation:

Keywords: Tumor angiogenesis, oxidative stress, antiangiogenic therapy, reactive oxygen species, nitric oxide, small-molecule angiogenesis inhibitors, VEGF, hypoxia, sorafenib, sunitinib, E3 ubiquitin, factor inhibiting HIF, ETC, ascorbate, SnPPIX, HUVEC, TSP-1, Vasculogenesis, VASP, NOXs, angiotensin, VAS2870, PTK787, vatalanib, Thymidine Phosphorylase, trifluorothymidine, flavopiridol, fibrosarcoma, glioma, NSCLC, ZnPPIX treatment

Abstract: Historically, oxidative stress was recognized to contribute to cancer development uniquely by induction of genomic instability. However, recent research has provided multiple evidence that reactive oxygen species and other free radicals, such as nitric oxide, often produced at elevated levels within tumor tissue, may function as signaling molecules that initiate and/or modulate the different regulatory pathways involved in tumorigenesis and metastasis. This review will focus on the complex role of oxidative stress and redox signaling in cancer neovascularization, a process without which the tumor is unable to grow beyond few millimeters in size. Reactive oxygen species and nitric oxide affect cell responses to hypoxia, a major trigger of angiogenic switch in tumors and are important upstream regulators as well as downstream mediators of action of the most potent proangiogenic factor - vascular endothelial growth factor. We will discuss targeting the redox-regulated mechanisms for antiangiogenic anticancer therapy and focus on recent developments in small-molecule agents that have either completed clinical trials or show a great promise to be subjected to them. Modulation of redox species production, signaling and metabolism and/or manipulating cellular antioxidant responses represents a multitargeted therapeutic approach which may possibly overcome the limitations of single-agent antiangiogenic treatments and potentiate effects of standard methods.

Cite this article as:

Tertil Magdalena, Jozkowicz Alicja and Dulak Jozef, Oxidative Stress in Tumor Angiogenesis - Therapeutic Targets, Current Pharmaceutical Design 2010; 16 (35) . https://dx.doi.org/10.2174/138161210794454969