Cancer metabolism is a new and exciting field of biology that provides a fundamentally different approach to treating cancer.
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Cancer cells become addicted to certain fuel sources and inherently alter their cellular machinery to change how they consume and utilize nutrients such as the sugar glucose. Inhibiting key enzymes in cancer cell specific metabolic pathways has the potential to disrupt tumor cell proliferation and survival without affecting normal cells, thus providing a powerful new intervention point for discovery and development of novel targeted, cancer therapeutics. Agios believes that this is an entirely novel approach to treating cancer, and the company’s research is directed at identifying such metabolic targets and discovering medicines against them.
The metabolic rewiring of cancer cells can also be linked to specific genetic alterations in oncogenes (which are genes that transform normal cells into tumor cells) and tumor suppressor genes (which are genes that are antioncogenic) responsible for cell signaling. These mutations in signaling pathways can drive excessive uptake of nutrients and altered metabolic pathways, thereby causing cancer formation. This cross-talk between cell signaling and metabolism offers multiple opportunities to treat cancer by combining Agios therapies directed against metabolic enzymes with existing or emerging standards of care.
Key Research Illuminates the Potential for the Field of Cancer Metabolism
Fundamental differences in the metabolism of normal cells and rapidly proliferating cancer cells were first discovered by Otto Warburg more than 80 years ago – an observation that earned him the Nobel Prize. Only recently, however, have researchers begun to understand the precise biologic nature of these changes and that these altered metabolic processes can be a fundamental driver of tumor growth, rather than simply being a consequence of the cancer.
Recent research has demonstrated that cancer cells have developed highly regulated processes for nutrient consumption and utilization. Cancer cells alter their consumption and the way they process sugars, fats, amino acids and other energy sources to satisfy the demands of continuous proliferation. Together, these proliferation-supporting processes represent a cellular phenomenon called “metabolic rewiring.”
The development of cancer metabolism inhibitors and the possibility of combining them with existing therapeutic approaches could have a profound anticancer effect and fundamentally change the treatment of cancer. Cancer metabolism therefore represents a powerful new lens for studying cancer that complements traditional areas of focus such as genetics and signaling.
Cancer Metabolism Review Articles by Agios Founders & Collaborators
Scientific publications from Agios founders and collaborators featuring significant discoveries and reviews in the field of cancer metabolism include:
- "Rethinking the Regulation of Cellular Metabolism." Thompson CB., Cold Spring Harbor Symposia on Quantitative Biology, 2012
- "Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?" DeBerardinis RJ., Thompson CB., Cell, 2012
- "Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate." Ward PS., Thompson CB., Cancer Cell, 2012
- "Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation." Vander Heiden et al, Science, 2009
- "PKM2 tyrosine phosphorylation and glutamine metabolism signal a different view of the Warburg effect." Dang C., Science Signaling, 2009
- "The biology of cancer: metabolic reprogramming fuels cell growth and proliferation." DeBerardinis et al., Cell Metabolism, 2008
- "Metabolic targeting as an anticancer strategy: dawn of a new era?" Pan and Mak, Science Signaling, 2007