The role of inflammation in head and neck cancer.

ABSTRACT

Cancer-related inflammation is considered the "seventh hallmark of cancer"; numerous studies demonstrate that tumors develop and progress within inflammatory diseases. Central to the development of cancer are genetic changes that endow these cancer cells with many of the hallmarks of cancer, such as self-sufficient growth and resistance to anti-growth and pro-death signals. However, while the genetic changes that occur within cancer cells themselves, such as activated oncogenes or dysfunctional tumor suppressors, are responsible for many aspects of cancer development, they are not sufficient. Tumor promotion and progression are dependent on ancillary processes involving cells of the tumor environment that are not necessarily cancerous themselves. Infiltration of immune cells facilitates tumor development through the production of factors that promote carcinogenesis and by enabling tumors to evade the host immune response. Small molecules including cytokines, chemokines, and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis, and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation and provides structural support to developing tumors. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumorigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients, and growth factors to rapidly dividing cells and providing a mechanism for metastatic spread. This review will discuss the reflexive relationship between cancer and inflammation with particular focus on how by considering the role of inflammation in physiologic processes such as the maintenance of tissue homeostasis and repair may provide a logical framework for understanding the connection between the inflammatory response and cancer. The cells and molecules outlined here represent potential targets for the treatment of head and neck cancer.