The Tumor Microenvironment: Characterization, Redox Considerations, and Novel Approaches for Reactive Oxygen Species-Targeted Gene Therapy

POLICASTRO L; IBAÑEZ IL; NOTCOVICH C; DURÁN H; PODHAJCER OL

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

Lugar: New York; Año: 2013 vol. 19 p. 854 - 895

1523-0864

The tumor microenvironment is a complex system that involves the interaction between malignant and neighbor stromal cells embedded in a mesh of extracellular matrix components. Stromal cells (fibroblasts, endothelial and inflammatory cells) are co-opted at different stages to help malignant cells invade surrounding extracellular matrix and disseminate. Malignant cells have developed adaptive mechanisms to survive under the extreme conditions of the tumor microenvironment such as restricted oxygen supply (hypoxia), nutrients deprivation and a prooxidant state among others. These conditions could be eventually used to target drugs that will be activated specifically in this microenvironment. Preclinical studies have shown that modulating cellular/tissue redox state by different gene therapy approaches were able to control tumor growth. In this review we describe the most relevant features of the tumor microenvironment, addressing reactive oxygen species-generating sources that promote a prooxidative microenvironment inside the tumor mass. We describe different gene therapy approaches that promote either decreased or exacerbated prooxidative microenvironment, and those that make use of the differential levels of ROS between cancer and normal cells to achieve tumor growth inhibition.