Targeting Tumor Microenvironment for Cancer Therapy

• Published in: International journal of molecular sciences 2019-02, Vol.20 (4), p.840
• Main Authors: Roma-Rodrigues, Catarina, Mendes, Rita, Baptista, Pedro V, Fernandes, Alexandra R
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apoptosis; c-Myc protein; Cancer; Cancer therapies; Carcinogenesis; Carcinogens; Chemotherapy; Clinical trials; Collagen; Drug delivery; Drug development; Drugs; Elastin; Epidermal growth factor; Epidermal growth factor receptors; Extracellular matrix; Fibronectin; Glycoproteins; Growth factors; Homeostasis; Humans; Hyaluronic acid; Hypoxia; Immune system; Immunosuppressive agents; Metabolism; Metastases; Metastasis; Models, Biological; Molecular Targeted Therapy; Mutation; Myc protein; Nanomedicine; Neoplasms - pathology; Neoplasms - therapy; Neovascularization, Pathologic - therapy; p53 Protein; Proteins; Proteoglycans; Radiation therapy; Review; Surgery; Tumor Microenvironment; Tumors; Vascularization
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20040840

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, "tumor on a chip" or multicellular tumor-spheroids.