Calorie restriction, and related approaches such as protein restriction, tend to improve the outcomes for cancer patients, making cancers more vulnerable to therapies by reducing the normally rampant replication of cancer cells. Here, researchers explore the role of mTOR signaling in the mechanisms underlying this effect, finding the link between dietary intake of amino acids and mTOR activity in cell growth. Manipulating these mechanisms isn’t enough on its own to deal with cancer, but there is a lot to be said for low cost improvements to the odds of success for patients undertaking any form of cancer therapy.
Researchers found in cells and in mice that a low-protein diet blocked the nutrient signaling pathway that fires up a master regulator of cancer growth. The regulator, mTORC1, controls how cells use nutritional signals to grow and multiply. It’s highly active in cancers with certain mutations and is known to cause cancer to become resistant to standard treatments. A low-protein diet, and specifically a reduction in two key amino acids, changed the nutritional signals through a complex called GATOR.
GATOR1 and GATOR2 work together to keep mTORC1 in business. When a cell has plenty of nutrients, GATOR2 activates mTORC1. When nutrients are low, GATOR1 deactivates mTORC1. Limiting certain amino acids blocks this nutrient signaling. Previous efforts to block mTORC1 have focused on inhibiting its cancer-causing signals. But these inhibitors cause significant side effects – and when patients stop taking it, the cancer comes back. The study suggests that blocking the nutrient pathway by limiting amino acids through a low-protein diet offers an alternative way to shut down mTORC1.
Researchers confirmed their findings in cells and mice, where they saw that limiting amino acids stopped the cancer from growing and led to increased cell death. They also looked at tissue biopsies from patients with colon cancer, which confirmed high markers of mTORC correlated with more resistance to chemotherapy and worse outcomes.