Finding the right target in cancer is not an easy task. Among a number of challenges are the tumor microenvironment and the molecular, cellular, and metabolic complexities.
Cancer cells exist with the help of other "resident" cell types. Other cell types are found on the tumor periphery or mixed with tumor cells. These other types of cells include immune cells (microglial cells, macrophages, dendritic cells, natural killer cells, T cells, etc.) and fibroblasts.
Macrophages are tissue-resident immune cells that are capable of eliminating "unwanted cells" such as infected cells or tumor cells through phagocytosis. As cancer progresses, macrophages are transformed from "engulfers" to "enablers" by becoming tumor-associated macrophages (TAMs). TAMs have been reported to promote cancer cell growth, angiogenesis, and metastasis.
Under normal physiological conditions in response to inflammation, fibroblasts migrate to the tissues, where they proliferate and serve as "bricks and mortar" for new tissue generation. Under cancerous conditions, however, fibroblasts become "cancer-associated fibroblasts" (CAFs) to carry out tasks in aiding tumor growth and migration.
Within the Glioblastoma multiforme (GBM) tumor microenvironment, TGFβ is at the center stage, crosslinking different signaling pathways to enable and augment growth and survival capabilities.
The GBM tumor microenvironment is illustrated in Figure 6 below.
