A New Approach to Cancer Therapy: The Tumor Microenvironment as Target
Pp. 3-68 (66)
Reto A. Schwendener and Sibel Mete
Solid tumors grow within a complex microenvironment composed of diverse
cell types such as fibroblasts, endothelial cells, mast cells, macrophages and immune
cells that are attracted by tumor cell derived factors and embedded in an extracellular
matrix. Molecular and cellular interactions between epithelial cells and cells
surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay
or impede tumor growth, the tumor microenvironment (TME) is increasingly being
explored as a potential therapeutic target for which novel strategies are developed.
This article reviews how key interactions between tumor cells and surrounding
mesenchymal and immune cells in the TME can promote tumor progression and it
highlights cellular and molecular elements that might represent novel therapeutic
targets. Special emphasis is given on therapies targeted towards tumor-associated
macrophages. As main class of drugs the bisphosphonates are covered with their
properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor
growth inhibiting and immunocompetent microenvironment. Properties and advantages
of liposome-encapsulated bisphosphonates as macrophage depleting or modulating
agents as well as the latest developments towards clinical applications of compounds
targeting cellular and molecular components of the TME are described and reviewed.
Adjuvant cancer therapy, bisphosphonates, clodronate, fibroblasts,
immune cells, immunotherapy, liposomes, macrophage depletion, macrophages,
myeloid derived suppressor cells, neutrophils, repolarization, reprogramming,
stromal cells, stromal interactions, therapeutic targets, tumor associated
macrophages, tumor associated neutrophils, tumor microenvironment.
Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.