Chemotherapy and Inflammatory Cytokine Signalling in Cancer Cells and theTumour Microenvironment.

Abstract

Cancer is the result of a cell's acquisition of a variety of biological capabilities or 'hallmarks' as outlined by Hanahan and Weinberg. These include sustained proliferative signalling, the ability to evade growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and the ability to invade other tissue and metastasize. More recently, the ability to escape immune destruction has been recognized as another important hallmark of tumours. It is suggested that genome instability and inflammation accelerates the acquisition of a variety of the above hallmarks. Inflammation, is a product of the body's response to tissue damage or pathogen invasion. It is required for tissue repair and host defense, but prolonged inflammation can often be the cause for disease. In a cancer patient, it is often unclear whether inflammation plays a protective or deleterious role in disease progression. Chemotherapy drugs can suppress tumour growth but also induce pathways in tumour cells that have been shown experimentally to support tumour progression or, in other cases, encourage an anti-tumour immune response. Thus, with the goal of better understanding the context under which each of these possible outcomes occurs, recent progress exploring chemotherapy-induced inflammatory cytokine production and the effects of cytokines on drug efficacy in the tumour microenvironment will be reviewed. The implications of chemotherapy on host and tumour cytokine pathways and their effect on the treatment of cancer patients will also be discussed.