Scientists discovered that kidney cancer cells produce a harmful substance called MMA that helps tumors grow by changing immune cells in the body. When they tested a low-protein diet and a new drug called MC3138 in lab and animal studies, both approaches slowed down tumor growth. This research suggests that combining dietary changes with this new medicine might help kidney cancer patients, especially those with high levels of MMA. While these results are promising, more testing in humans is needed before doctors can recommend this treatment.

The Quick Take

  • What they studied: How a chemical called methylmalonic acid (MMA) that kidney cancer cells make affects tumor growth and whether changing diet or using a new drug can stop it
  • Who participated: Laboratory cell cultures and animal models (mice) with kidney cancer; no human patients were directly tested in this study
  • Key finding: MMA produced by kidney cancer cells activates immune cells in ways that help tumors grow, but a low-protein diet or a new drug called MC3138 can block this process and slow tumor growth
  • What it means for you: This research may lead to new treatment options for kidney cancer patients, but it’s still in early stages. People with kidney cancer should continue following their doctor’s current treatment plans while researchers work toward human trials of these approaches

The Research Details

Researchers used advanced laboratory techniques to analyze kidney cancer cells and identify which chemicals they produce in abnormal amounts. They found that kidney cancer cells make too much of a substance called MMA because they lack an enzyme that normally breaks it down. The team then studied how this MMA affects immune cells called macrophages in the tumor environment. They tested two approaches: feeding mice a diet low in branched-chain amino acids (building blocks of protein) and treating them with an experimental drug called MC3138 that removes the MMA chemical modification. Both approaches were tested in laboratory dishes with cancer cells and in living mice with kidney tumors to see if they could slow cancer growth.

Understanding how cancer cells change their metabolism (how they use nutrients) is important because it reveals new ways to attack tumors. By finding that MMA is a key player in kidney cancer growth, researchers identified a specific target that could be blocked with diet or medicine. This approach is valuable because it targets both the cancer cells and the immune environment around them, potentially making treatment more effective.

This is laboratory and animal research, which is an important first step but doesn’t directly prove the approach will work in humans. The study was published in a respected scientific journal, suggesting it passed expert review. However, results in mice don’t always translate to humans, and the specific drug MC3138 would need to be tested in human clinical trials before it could be used as a treatment. The research is well-designed within its scope but represents early-stage discovery rather than proven therapy.

What the Results Show

The researchers found that kidney cancer cells produce abnormally high levels of MMA, a chemical that accumulates around tumors. This MMA activates a signaling pathway in immune cells that causes them to become ‘helper’ cells for the tumor instead of fighting it. When mice were fed a low-protein diet or treated with MC3138, the amount of MMA decreased, immune cells stopped helping the tumor, and tumor growth slowed down significantly. The effect was dose-dependent, meaning higher doses of MC3138 or stricter dietary restrictions had stronger effects on slowing tumor growth.

The study identified the exact molecular mechanism of how MMA works: it attaches to a protein called USP36, which then can’t do its normal job of controlling other proteins involved in tumor growth. This detailed understanding helps explain why blocking MMA production is effective. The research also showed that the low-protein diet and MC3138 drug worked through the same pathway, suggesting they could potentially be combined for better results.

Previous research showed that kidney cancer cells have abnormal metabolism, but this study is among the first to identify MMA as a specific culprit and to show how it helps tumors grow by changing immune cells. The findings build on earlier work showing that immune cells in tumors can either fight cancer or help it grow, depending on signals they receive. This research adds a new piece to the puzzle by identifying MMA as one of those signals.

This study only tested the approaches in laboratory cells and mice, not in humans. The results may not translate directly to people because human bodies are much more complex. The study didn’t test whether the low-protein diet alone (without the drug) would work in humans or what side effects might occur. The research also didn’t compare these approaches to current kidney cancer treatments to see which might be more effective. Additionally, the study focused on kidney cancer cells with specific characteristics, so results might not apply to all kidney cancer patients.

The Bottom Line

This research suggests that kidney cancer patients with high MMA levels might benefit from a low-protein diet combined with MC3138 therapy in the future (moderate confidence level, pending human trials). However, this is not yet a recommended treatment. Current kidney cancer patients should continue working with their oncologists on proven treatments while this research progresses toward human testing.

This research is most relevant to people with clear-cell renal cell carcinoma (the most common type of kidney cancer), particularly those with elevated MMA levels. It may eventually be relevant to other cancer types with similar metabolic changes. People without kidney cancer don’t need to make dietary changes based on this research. Healthcare providers and kidney cancer researchers should pay attention to these findings as they plan future studies.

If MC3138 moves forward to human trials, it would typically take 5-10 years before it could become an available treatment. The low-protein diet approach could potentially be tested sooner in clinical settings. Patients should not expect immediate changes to their treatment options but can stay informed about clinical trials testing these approaches.

Want to Apply This Research?

  • For users interested in kidney cancer research, track branched-chain amino acid intake (from protein sources like meat, eggs, and dairy) and monitor any clinical trial opportunities for MMA-targeting therapies in your area
  • Users could set a reminder to review their protein intake distribution throughout the day and explore plant-based protein sources as an alternative to animal proteins, while discussing any dietary changes with their healthcare provider
  • Long-term tracking could include monitoring energy levels and muscle strength if reducing protein intake, periodic check-ins with healthcare providers about new kidney cancer treatment options, and setting alerts for clinical trial announcements related to MMA and kidney cancer

This research describes laboratory and animal studies, not human clinical trials. The findings are promising but not yet proven safe or effective in people. Anyone with kidney cancer should continue following their doctor’s current treatment recommendations and discuss any interest in dietary changes or experimental therapies with their oncology team before making changes. This article is for educational purposes and should not be used to make medical decisions. Always consult with qualified healthcare providers about cancer treatment options.