Relevance of tumor microenvironment for progression, therapy and drug development

Tumor interstitium exhibits a microenvironment that differs from corresponding normal tissues. Tumor phenotype shows, for example, an elevated intracellular pH (pH(i)), a lowered extracellular pH (pH(e)), a low oxygen concentration and low glucose levels. These differences are caused by cell biological (so called intrinsic) factors, e.g. a higher acidification rate, as well as by more systemic (extrinsic) factors, e.g. poor tumor vascularization. They represent important factors for invasiveness, immune suppression and proliferation, and they imply possibilities for diagnosis, prognosis and therapy. We have developed an experimental data-based computer model, which has simulated the potential role of metabolic effects on tumor progression. We show an experiment on cellular metabolism demonstrating the immunosuppressive impact of low pH. on peripheral blood mononuclear cells. Finally, we review important findings on the tumor microenvironment leading to possibilities for therapy which are currently evolving and which promise higher effectiveness for cancer therapy. (C) 2004 Lippincott Williams Wilkins.