The tumour microenvironment as an integrated framework to understand cancer biology

Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, giving rise to a new field of study and clinical management. Nowadays, somatic mutation theory is complemented with study of TME components such as the extracellular matrix, immune compartment, stromal cells, metabolism and biophysical forces. In this review we examine recent studies in this area and complement them with our own research data to propose a classification of stromal changes. Exploring these avenues and gaining insight into malignant phenotype remodelling, could reveal better ways to characterize this disease and its potential treatment. •New information in the TME field offer improved prognostic and predictive biomarkers.•Tumour microenvironment is a determinant of cancer progression and therapy-response.•The biophysical and bioelectrical properties of cancer cells/TME drive malignancy.•Intratumoral heterogeneity depends on the metabolic alterations and nutrient availability.•Classification in three stromal alteration grades provides a new framework in cancer biology.