The Warburg Effect: Can Cancer Be Starved of Sugar?

The Warburg effect takes its name from Otto Warburg’s discovery in the 1920s that tumors take up huge amounts of glucose, which they ferment into lactate rather than respire. He postulated that dysfunctional mitochondria might be to blame, and that aerobic glycolysis is the primary cause of cancer.

Since then, thousands of papers have been published with multiple explanations of the effect proposed. Among them, a 2016 review noted, is “an adaptation mechanism to support the biosynthetic requirements of uncontrolled proliferation,” as “a tradeoff to support biosynthesis,” in acidification of the tumor microenvironment, and “in direct signaling functions to tumor cells.”³

That led the review’s authors to conclude that “it is likely we will require a better understanding of the biology of Warburg Effect if therapeutic advances are to be made in treating and preventing cancer using dietary and pharmacological intervention in metabolism, and in using glucose metabolism to manipulate the immune system, which are currently subjects of intense interest.”

The connection between Ras proteins and cancer is, however, much better understood.

As a 2011 overview stated: “Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development.

“Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis.”⁴

Sugar has long been linked to cancer indirectly through, for example, well-established associations between obesity and cancer. A 2014 policy paper by the American Society of Clinical Oncology (ASCO) noted that “obesity is a major under-recognized contributor to the nation’s cancer toll and is quickly overtaking tobacco as the leading preventable cause of cancer.”⁵