Expert view: Creating metabolic liabilities to target cancer

As the pace of genetic approaches to combating cancer slows, researchers are focusing on novel approaches to identify and create metabolic liabilities in cells. Cancer cells rewire their metabolism to survive and proliferate rapidly; however, there is no single metabolic phenotype that enables this rewired state.

In fact, many nutrient uptake and oxidation pathways are altered, and this varies by cancer cell type.  These findings are challenging the notion that “cancer cells are glycolytic” because it’s just not that simple.  As a result, many of these metabolic pathways are now considered to be good targets for new therapies. 

A more complete view of energy metabolism is providing new understanding to the true and varied metabolic requirements of tumor cells.  Our recent examination of 18 cancer cell lines demonstrated that there is remarkable heterogeneity in the metabolic poise of the cells. For example, on a per-cell basis, total ATP demand varied almost 5-fold between the highest and lowest cell types measured.  Moreover, the relative contribution of glycolysis to ATP production varied from as much as 80% to as little as 10% (in Hs578 and BT474 cell lines respectively).  Importantly, this type of information could be used to identify metabolic liabilities in specific cancer cell types; proliferation is markedly decreased in the presence of anti-glycolytic compounds, but only in cell lines with significant reliance on glycolytic ATP production. 

In sum, as scientists seek new drug targets, cell metabolism is a key area of research which must be considered.  Biotech startups are now targeting the pathways that enable metabolic rewiring of cancer cells as they work to create the next novel anti-cancer drug.  Companies such as Navitor, Rheos, and others are at the forefront of this field and are the ones to watch as new metabolic liabilities are uncovered.

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