Cancer cells develop as a result of sustained accumulation of genetic and epigenetic changes in cells that promote uncontrolled replication of cells and escape the detection by the immune system. Beside cancer cells, the nonneoplastic cells of the tumor microenvironment, such as stroma cells and blood vessels, are a key determinant of cancer biology. As cancer cells grow, they influence surrounding tissues (the so-called tumor-stroma interaction), which in turn has a major impact on cancer cell invasion, survival, and progression.

Tumor-stroma interaction is mediated by a complex and dynamic crosstalk involving cytokines, chemokines, growth factors, enzymes, microRNAs, and other effector molecules. As our understanding of the role of tumor microenvironment grows, the complexity of the interactions between cancer cells and their surrounding tissues becomes more and more evident. Signalling and effector molecules not only passively diffuse the extracellular matrix to reach their target cell(s) but are, for example, transported via specialized particles such as oncosomes. Even though much progress has been made in understanding the importance of tumor microenvironment in cancer, there still exist several unanswered questions. A major limitation that affects functional studies of the tumor microenvironment is the lack of appropriate In vitro or in vivo models of tumor microenvironment for several cancers. The rapid progress in understanding the role of tumor microenvironment in cancer pathogenesis depends on a multidisciplinary approach involving basic scientist, bioengineers, and clinicians and development of appropriate In vitro and in vivo models of tumor growth, invasion, extracellular matrix remodelling, angiogenesis, and inflammation.

We believe that this special issue on tumor microenvironment will evoke greater interest among the cancer biologists. We invite researchers in this field to contribute original research as well as review articles that will enhance our continuing effort to understand the biology and role of tumor microenvironment in cancer.

Potential topics include, but are not limited to:

• In vitro and in vivo models of tumor microenvironments and their applications in the study of the biology of cancer cell-stroma interaction
• Emerging roles of functionally important cellular components such as microRNA, immune modulators, epigenetic regulators, and oncosomes in cancer cell-tumor microenvironment interaction
• Tumor microenvironment targeted anticancer strategies such as chemotherapy, chemoimmunotherapy, and immunotherapy