The tumor suppressor PTEN in control of the tumor microenvironment, hypoxia-dependent angiogenesis and tumor immunosuppression
Résumé
The challenge of fighting tumor hypoxia leads to new approaches in angiogenesis-based strategies. Revisiting the theory according to which angiogenesis should be destroyed, which failed because of raising tumor resistance, is necessary. It appears that alleviation of hypoxia can be reached thanks to the molecular mechanism involving myo-inositoltrispyrophosphate which normalizes vessels in tumor by increasing oxygen tension. It also brings a stable normalization of the vessels, by add ressing its action to PTEN in endothelial cells and regulating their growth. PTEN is a tumor suppressor which is most frequently affected in cancer. This review focuses on the fundamental properties of PTEN, which controls the PI3K-mTOR pathway as well as its nonphosphatase activity as a tumor suppressor and on the strategies used to treat cancer by activating PTEN. It points to the potential and means of raising PTEN activity in the tumor angiogenesis as a new adjuvant therapeutic modality.