Study Challenges Long-Standing Concept in Cancer Metabolism

Scientists have discovered that lactate provides a fuel for growing tumors, challenging a nearly century-old observation known as the Warburg effect.

Lactate is the conjugate base of lactic acid. Lactic acid is found primarily in sour milk products, such as koumiss, laban, yogurt, kefir, and some cottage cheeses. Image credit: Schwäbin/Wikipedia (CC BY-SA 3.0 de)

Scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) have discovered that lactate provides a fuel for growing tumors, challenging a nearly century-old observation known as the Warburg effect.

This new finding may represent a major shift in how researchers view cancer metabolism and open a new avenue of study for therapies and imaging techniques for lung cancer, which is the leading cause of carcinoma deaths worldwide.

The oldest observation in cancer metabolism, the Warburg effect, says that lactate is a waste product of the tumor. This concept has driven the vast amount of research in the field.

The Warburg effect, named after the German cancer biologist Otto Warburg, has three main components: rapid glucose uptake, reduced glucose oxidation even when oxygen is present, and secretion of lactate as a waste product.

In the study, CRI researchers showed lactate is not only a waste product but also acts as a fuel source consumed by lung cancer cells growing in patients and mice. Combined with a previous study from the DeBerardinis lab that showed activated glucose oxidation in tumors, the results of this study are challenging the tenets of the Warburg effect.

Lactate is one of the fuels that supports growth, proliferation, and maybe even lung cancer metastases. Cancer metabolism is clinically actionable, and understanding the lactate pathway could help us find therapeutic targets for lung cancer. Lactate uptake could also have predictive value when used as an imaging tracer.

Additional findings in the study suggest a potential link between lactate use and cancer aggression.

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