Metabolic Symbiosis

Nirogy Therapeutics, Boston

Metabolic Symbiosis

Once believed to be simply a waste product, Lactate has crucial biological functions that are now actively being investigated. Lactate has been well recognized as an immune suppressor. Additionally, certain tumor types preferentially use lactate as the primary energy source over glucose. Cancer is often plagued by heterogeneity, meaning a single tumor does contain vastly different cell populations – each with its own unique way to grow, spread by reprogramming metabolic tumor and immune microenvironment (mTIME).

Tumors are largely hypoxic, and cells located farther away from blood vessels have low or no oxygen, which force those “hypoxic tumor cells” to preferentially utilize glucose. Lactate produced and exported by them via glycolysis into the TME is taken up by “oxidative tumor cells” located proximal to blood vessels as the food source, thus creating a “metabolic symbiosis” between phenotypically different cancer cells within the tumor. Similarly, tumor cells recruit surrounding stromal cells such as “cancer-associated fibroblasts (CAFs)” to produce lactate for their energy needs. This process also creates a “metabolic symbiosis” between cancer cells and surrounding non-transformed cells in the TME. Overall, the metabolic symbiosis mechanism in the TME effectively promotes rapid tumor growth and metastasis.

Nirogy’s dMCTi can disrupt this symbiotic relationship among various cell types in the TME and prevent tumor growth by blocking both MCT1 and MCT4.

Nirogy Lactate Metabolic Symbiosis chart

Further Readings

*Simon Schworer, Santhosha A. Vardhana, Craig Thompson, “Cancer Metabolism Drives a Stromal Regenerative Response”, Cell Metabolism (2019), 29(3), 576-591.

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Vincent P. Sandanayaka, Ph.D.


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