Changing diet kills cancer cells, overcomes drug resistance

Changing diet kills cancer cells, overcomes drug resistance

Green staining shows that mTORC1 is significantly increased by disruption in GATOR1 in a mouse model of colon cancer. Photo: Sumeet Solanki

A change in diet could be the key to boosting colon cancer treatment, a new study from the University of Michigan’s Rogel Cancer Center suggests.

Evil cell need nutrients to survive and thrive. 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 sensor cascade and turn off mTORC1.

While mTORC1 is known to be hyperactive in colon cancerThe key question is whether colon tumors hijack nutrient-sensing pathways to activate the master regulator.

“In the colon cancer, when you reduce the nutrients available in the tumor, the cells won’t know what to do. Without nutrients to grow, they go through a kind of crisis, resulting in dead cells“, said senior author Yatrik M. Shah, Ph.D., 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 are published in 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 specifically reducing two major factors Amino Acidsaltered 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.

Changing diet kills cancer cells, overcomes drug resistance

Abstract graphic. Credit: Gastroenterology (2022). DOI: 10.1053/j.gastro.2022.11.014

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.” Ph.D., a research investigator at the Rogel Cancer Center.

The researchers confirmed their findings in cells and mice, where they found that restricting amino acids stopped 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 have muscle weakness and weight lossthat protein restriction can be frustrating.

“Put cancer patient on a long-term protein-deficient diet is not ideal. But if you can find key times – such as at the start of chemotherapy or radiation – when a patient can go on a low-protein diet for a week or two, then we have the potential to increase effectiveness of those treatments,” Shah said.

Further research will refine this concept of therapeutic windows for amino acid restriction. The researchers will also seek to understand how these pathways confer resistance and whether an inhibitor can block GATOR complexes.

More information:
Sumeet Solanki et al., Amino acid sensing disorders promote colorectal cancer growth and metabolic reprogramming leading to chemoresistance., Gastroenterology (2022). DOI: 10.1053/j.gastro.2022.11.014

quote: Changing diet causes cancer cell death, overcoming drug resistance (2022, Nov 18) accessed Nov 20, 2022 from -dietary-starves-Cancer-cells- Treatment.html

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