Tumour-microenvironmental interactions: paths to progression and targets for treatment

Primary human tumours can often be eradicated by surgery if detected early; however metastatic disease renders complete cure less likely and the development of resistance to therapy results in tumour escape and increased risk of death. Interactions of tumour cells with each other, surrounding normal cells and extracellular matrix or basement membrane components are crucial to all stages of cancer progression. Changes in both cell–cell and cell–substrate proteins are linked to tumour cell migratory and invasive ability, induction of angiogenesis (on which sustained tumour growth and dissemination depends) and apoptosis resistance in response to drugs or radiotherapy. Hypoxia within solid tumours is a key driver of many aspects of progression, and may also nurture cancer stem-like cells which are increasingly linked to relapse and treatment failure. This review will briefly outline the cellular and molecular mechanisms underlying tumour progression, focussing on the acquisition of metastatic capacity and resistance to therapy.