Role of Tumour Microenvironment in Chemoresistance

Abstract

Preclinical and clinical findings indicate multiple tumour micro-environmental factors, including growth factors, cytokines, cell-cell and cell-matrix adhesion molecules and hypoxia, protect solid tumours from therapeutic interventions. Experimental evidence have defined some of the resistance mechanisms, which have led to the development of innovative approaches aiming at specific targets. While some of these newer approaches have yielded therapeutic benefits in selected tumour types, considerable challenges remain in the management of the majority of patients with solid tumours. This chapter reviews the various tumour microenvironmental factors that contribute to drug resistance. These factors exert their effects through direct promoting resistance effectors and/or indirectly modulating other environmental factors. Furthermore, cooperative regulation, cross-talk and redundancy at different levels of signaling cascades affect the tumour progression and drug resistance, and can diminish the effectiveness of the single target therapeutic approach. A better understanding of the intersecting resistance pathways has the potential of leading to new therapeutic paradigms aiming at multiple targets, in order to overcome the microenvironment-conferred survival advantage to tumour cells.