Chapter 11 . General conclusions and future perspectives

The normalization of the tumor ecosystem, consisting in many different cell types and components, is an important new tool for cancer treatment. This chapter discusses the potential targets within the tumor microenvironment (TME) with pharmacological perspective on tumor vascularization and optimization of cancer treatments: hypoxic, acidic and oxidative environment responsible for angiogenic switch and chaotic neovascularization; switch of normal ECs (NECs) to tumor ECs (TECs) in term of cell behavior, metabolism and signaling; cancer associated fibroblasts (CAFs) mainly responsible for angiogenic factor release and processing of the extracellular matrix (ECM); macrophage recruitment in the TME to become tumor associated macrophages (TAMs) and differentiation toward M2 phenotype; normalization of the tumor vasculature; activation of the antitumoral activity by immune cells; miRNAs and epigenetic determinants. The combination of therapies targeting different stromal components, together with traditional antitumor agents, represents the key element to impair cancer progression. Ongoing studies in the field which focus on studying the TME with an integrative approach bear the potential to significantly control tumor angiogenesis and broaden the spectrum of current anticancer treatments.