According to a recent study conducted by the University of Michigan Rogel Cancer Center, cutting off sustenance to cancer cells may be the key to beating treatment resistance.
A new study from the University of Michigan Rogel Cancer Center has found that altering the diet could be the key to improving colon cancer treatment, by depriving cancer cells of the sustenance they need to resist treatment. Cancers require different nutrients in order to flourish and grow.
One of the major molecules that senses nutrients in a cell is the mTORC1 protein. This master regulator of cell growth can detect the presence of different nutrients. It allows cells to expand and multiply. When nutrient sources are scarce the nutrient-sensing cascade switches off and mTORC1 is deactivated.
Researchers have long known that mTORC1 is overactive in colon cancer. But the question remains. Do colon tumors take advantage of nutrient-regulating pathways to activate the main controller?
“In colon cancer, without the nutrients to grow, they undergo a kind of crisis, which leads to massive cell death,” said senior author Yatrik M. Shah, Ph.D., Horace W. Davenport Collegiate Professor of Physiology at Michigan Medicine.
Study on dietary alterations:
Scientists discovered in cell cultures and mouse models that a reduction in dietary protein caused a block in the nutrient signaling pathway that activates the master regulator of cancer growth. These discoveries have been published in Gastroenterology.
mTORC1, which is responsible for how cells interpret nutritional signals and proliferate, is frequently overexpressed in cancer cells, making them resistant to standard treatments. Further study revealed that reducing two specific amino acids affects the GATOR complex, which in turn modifies the nutritional signals.
GATOR1 and GATOR2 collaborate to create an environment where mTORC1 can thrive. When the cell has more than enough nutrients, GATOR2 switches on mTORC1. When there are no resources available, GATOR1 shuts it down. Limiting specific amino acids can also prevent it from receiving the essential nutrient signaling.
Earlier attempts to inhibit the cancer-causing signals of mTORC have had a range of concerning side effects, making them a less desirable choice.
The results of the study propose that blocking the nutrient pathway by cutting back on certain proteins through a low-protein diet could offer a viable alternative to shutting down mTORC.
“We knew that nutrients were important in mTORC regulation but we didn’t know how they directly signal to mTORC. We discovered the nutrient signaling pathway is just as important to regulate mTORC as the oncogenic signaling pathway,” said study first author Sumeet Solanki, Ph.D., a research investigator at the Rogel Cancer Center.
Outcome of the diet change:
The study’s results were verified in both cellular and mammalian samples.
Limiting the essential amino acids stopped the growth of cancer and caused an increase in the death of cells. Examining tissue biopsies extracted from colon cancer patients also supported the findings. Higher levels of mTORC were associated with a greater resistance to chemotherapy and worse outcomes.
Solanki believes this could be used as a means to target treatment for those with this marker.
“A low-protein diet won’t be a standalone treatment. It has to be combined with something else, such as chemotherapy,” Solanki said.
The risk with a low-protein diet is that people with cancer often experience muscle weakness and weight loss, which limiting protein could exasperate, ” Shah said.
Scientists hope to discover more about the therapeutic window of limiting amino acids. And they want to know more about how their pathways create resistance to treatment.
The team will also investigate whether an inhibitor is capable of blocking the GATOR complexes.