Starving cancer by controlling cell proliferation
Understanding metabolisms of mammalian animals to prevent cancer progression
Chemotherapy is a common treatment for cancer. Unfortunately, while some cancer cells are sensitive to this method of treatment, other cancer cells are unresponsive. This begs the question: what causes this selectivity in cancer cells?
According to Matthew Vander Heiden, associate professor of biology, the key to addressing this challenge is understanding the metabolism of mammalian cells. His hypothesis marks a new era in cancer research, which previously focused solely on the genetic origins of cancer. “When I started my lab, the core hypothesis was that oncogenes, which cause cancer, would define metabolic differences among cancers. While this is true to a certain extent, our experiments indicated that cancer also takes on phenotypes based on the environment where the cancer is located,” said Vander Heiden, who currently serves as an associate director of the Koch Institute for Integrative Cancer Research.
Vander Heiden believes that, while cancer cells are different from healthy cells, they are not completely deviant, as cancer cells repurpose resources already available in the body. Rather, the cancer cells make alterations to existing metabolic processes — they take the normal metabolic pathway of an organ and adapt in a way that allows them to mass-proliferate. Chemotherapy is designed to target cancer cells that have metastasized to specific sites. However, when proliferation causes cancer cells to diffuse throughout the body, chemotherapy is no longer a reliable treatment option. The goal of the Vander Heiden group is to identify specific nutrients that cancer cells use to grow, which will then allow them to target individual cancer cells with a specificity beyond the limits of current treatment options.
To understand cancer metabolism, the Vander Heiden Lab mainly employs mass spectrometry to investigate metabolic pathways, which Vander Heiden described as a way “to visualize and measure how those metabolic transitions are happening within the cells.” Mass spectrometry is a technique that allows researchers to measure weight transformations in metabolites using their mass-to-charge ratio. Vander Heiden described an example: “if the cancer cell has several nutrients available to it, and you want to know which nutrient it eats, you can label a specific nutrient and see how it contributes to metabolic processes in cells.” Through this labeling technique, which measures how specific isotopes’ masses change over time, researchers can record which nutrients the cancer cells are dependent on, enabling them to target specific cancer cells for starvation.
Vander Heiden and his team see plausible solutions in inhibiting the cancer cells from proliferating by alternating the environment or the nutrients in which those malignant cells dwell. In addition to investigating how genes affect cancer development, as in traditional cancer research, “What we are really trying to understand is how genes plus the environment interact,” Vander Heiden explained.
Coming up on its tenth anniversary at MIT, the Vander Heiden Lab’s long-term goal is to adapt this technology towards understanding cancer cells in mammalian systems. As a researcher and a doctor, Vander Heiden also discussed the beauty of relating his discoveries directly to patients and drawing connections with the real world: “what I found most valuable is finding how metabolism and physiology work in the lab and seeing how this relates to things going on in the hospital.” The Vander Heiden Lab’s next step is to further investigate factors that constrain tumors from using metabolic pathways to grow, as well as to develop personalized medicine by understanding the different physiologies and metabolic processes that occur in each patient. Vander Heiden is looking forward to building a sophisticated picture of mammalian and cancer cell metabolic processes. As he put it, “The beauty of science is there’s another question, always a next bit of complexity in the problem.”