A new study of the University of Michigan Rogel Cancer Center has found that a change in diet could be the key to improving the colon cancer treatment. Cancer cells need nutrients to survive and grow. One of the most important nutrient sensing molecules in a cell is called mTORC1. Often called a master regulator of cell growth, it allows cells to sense different nutrients and therefore grow and proliferate. When nutrients are limited, cells reduce the nutrient sensing cascade and turn off mTORC1. The researchers found in cells and mice that a low-protein diet blocked the nutrient signaling pathway that activates a master regulator of cancer growth. The results are published in Gastroenterology. The regulator, mTORC1, controls how cells use nutritional signals to grow and multiply. It is very active in cancers with certain mutations and is known to make cancer resistant to standard treatments. A low-protein diet, and specifically a reduction in two key amino acids, changed nutritional signals through a complex called GATOR. GATOR1 and GATOR2 work together to keep mTORC1 in business. When a cell has a lot of nutrients, GATOR2 activates mTORC1. When nutrients are low, GATOR1 turns off mTORC1. Limiting certain amino acids blocks this nutrient signaling. Previous efforts to block mTORC have focused on inhibiting its cancer-causing signals. But these inhibitors cause significant side effects, and when patients stop taking them, the cancer returns. The study suggests that blocking the nutrient pathway by limiting amino acids through a low-protein diet offers an alternative way to shut down mTORC. The researchers confirmed their findings in cells and mice, where they saw that limiting amino acids stopped cancer growth and led to increased cell death. They also looked at tissue biopsies from colon cancer patients, confirming that high mTORC markers correlated with increased resistance to chemotherapy and poorer outcomes. The risk of a low protein diet is that people with cancer often experience muscle weakness and weight loss, limiting protein could exasperate.
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