A new study from the University of Michigan’s Rogel Cancer Center has found that one change your diet may be a key to strengthening the colon cancer treatment.
Cancer cells need nutrients to survive and grow. One of the most important nutrient-sensing molecules in cells is called mTORC1. Often referred to as the master regulator of cell growth, it allows cells to sense different nutrients and thus grow and proliferate. When nutrients are restricted, cells dial up the nutrient-sensing cascade and turn off mTORC1.
Although mTORC1 is known to be overactive in colon cancer, the key question is whether colon tumors hijack nutrient-sensing pathways for key regulator activation.
“In colon cancer, when you reduce the nutrients available in the tumour, the cells don’t know what to do. Without nutrients to grow, they go through a kind of crisis, which leads to cell death. series,” said lead author Yatrik. M. Shah, PhD, Horace W. Davenport Collegiate Professor of Physiology at Michigan Medicine.
The researchers found in cells and in mice that a low-protein diet blocked the nutrient signaling pathway that activates a key regulatory mechanism of cancer growth. The results were published in the journal Gastroenterology.
The regulator, mTORC1, controls how cells use nutritional signals to grow and multiply. It is highly active in cancers with certain mutations and is known to cause cancers to become resistant to standard treatments. A diet low in protein, and especially reduced in two key amino acids, altered nutritional signals through a complex called GATOR.
GATOR1 and GATOR2 work together to keep mTORC1’s business going. When a cell has plenty of nutrients, GATOR2 activates mTORC1. When nutrients are low, GATOR1 turns off mTORC1. Restricting certain amino acids will block this nutritional signal.
Previous efforts to block mTORC have focused on inhibiting its oncogenic signals. But these inhibitors cause significant side effects — and when patients stop taking them, the cancer comes back. Research shows that blocking the nutritional pathway by restricting amino acids through a low-protein diet provides another way to turn off mTORC.
“We know that nutrients play an important role in regulating mTORC, but we don’t know how they signal directly to mTORC,” said first author Sumeet Solanki. found that the nutrient signaling pathway is just as important for regulating mTORC as the oncogenic signaling pathway.” PhD, a research investigator at the Rogel Cancer Center.
The researchers confirmed their findings in cells and mice, where they found that limiting amino acids prevented cancer from growing and led to increased cell death. They also looked at tissue biopsies from colon cancer patients, confirming that elevated markers of mTORC correlated with greater resistance to chemotherapy and worse outcomes. This could offer direct treatment opportunities for patients with these signs, says Solanki.
“The low-protein diet will not be a stand-alone treatment,” says Solanki. It has to be combined with something else, such as chemotherapy.
The risk with low-protein diets is that people with cancer often experience muscle weakness and weight loss, which can exacerbate protein restriction.
“Putting cancer patients on a low-protein diet for long periods of time isn’t ideal. But if you can find the key times — like when chemotherapy or radiation therapy is started — when the patient can be in control of the disease.” By taking a low-protein diet for a week or two, we could potentially increase the effectiveness of those treatments,” says Shah.
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