How the ageing microenvironment influences tumour progression

Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health problem. It is estimated that, by 2050, more than 20% of the world’s population will be over the age of 60 — the economic, healthcare and financial burdens this may place on society are far from trivial. In this Review, we address the role of the ageing microenvironment in the promotion of tumour progression. Specifically, we discuss the cellular and molecular changes in non-cancerous cells during ageing, and how these may contribute towards a tumour permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. We also discuss the contribution of these changes to responses to cancer therapy as ageing predicts outcomes of therapy, including survival. Yet, in preclinical studies, the contribution of the aged microenvironment to therapy response is largely ignored, with most studies designed in 8-week-old mice rather than older mice that reflect an age appropriate to the disease being modelled. This may explain, in part, the failure of many successful preclinical therapies upon their translation to the clinic. Overall, the intention of this Review is to provide an overview of the interplay that occurs between ageing cell types in the microenvironment and cancer cells and how this is likely to impact tumour metastasis and therapy response. The majority of cancers arise in individuals over the age of 60. This Review discusses how ageing tissues through changes in the extracellular matrix as well as in the functions of fibroblasts and immune cells can impact tumour initiation, progression and response to therapy.