In the 1920s Warburg first observed that "tumors have a remarkable capacity to ferment glucose even in the presence of adequate oxygen.” This altered metabolism of glucose has been shown to be both a cause and consequence of alterations in the physical tumor microenvironment including hypoxia and acidosis. However, in the modern molecular era, interest in this topic faded as summarized by Sidney Weinhouse: “Since our perspectives have broadened over the years, the burning issues of glycolysis and respiration in cancer now flicker only dimly.”
However, interest in the tumor metabolism has recently rebounded largely because of FdG-PET imaging which relies on increased glucose uptake to image primary and metastatic cancers. Thousands of clinical PET studies have now shown that the vast majority (>90%) of cancer exhibit increased glucose uptake. In fact, increased glucose uptake is a observed with a far greater frequency than any oncogene or tumor suppressor gene mutation.
We propose that the physical microenvironment, which is inextricably linked with tumor metabolism, plays a critical role in development and progression of cancers. Furthermore, iatrogenic perturbations of the physical microenvironment can alter tumor growth, invasion, and metastases.