Research Spotlight: Mapping Metastasis—How Nutrient Availability Shapes Breast Cancer’s Spread

Rakesh K. Jain, PhD, of the Mass General Brigham Cancer Institute and Harvard Medical School, is the co-corresponding author of a new paper published in Nature, “Nutrient requirements of organ-specific metastasis in breast cancer.”

Q: How would you summarize your study for a lay audience?

Breast cancer can spread—or metastasize—to many different parts of the body, but it’s not well understood why tumors grow better in some organs than others. We explored whether the nutrients available in different tissues help determine where cancer spreads. Using mouse models and advanced metabolic profiling, we measured nutrient levels across several organs and tested how depriving cancer cells of specific nutrients affected their ability to form metastases.

Surprisingly, we found that no single nutrient explains why breast cancer grows in one organ and not another. Instead, a combination of multiple nutrients and cancer cell characteristics work together to determine where tumors can thrive.

Q: What central question were you investigating?

We asked: Does the availability of nutrients in different tissues control where breast cancer metastasizes? More specifically, could limiting certain nutrients prevent cancer cells from growing in specific organs and are some nutrients more important than others?

Q: What methods or approach did you use?

First, we measured the levels of over 100 nutrients in the brain, plasma and various organs of mice to understand the “nutrient landscape” that cancer cells face when spreading. Then, we genetically modified breast cancer cells so they could no longer make specific nutrients, such as serine, arginine, or purines, and injected them into mice to see where they could and couldn’t grow.

This allowed us to test whether cancer cells fail to grow if they can’t make a nutrient that is missing in a specific organ. For instance, if a tumor can’t make serine and the brain is low in serine, does that prevent metastasis to the brain?

Q: What did you find?

We found that no single nutrient shortage could fully explain metastasis patterns. While some nutrients like purines were consistently essential for tumor growth across organs, others like amino acids (e.g., serine or arginine) showed variable effects depending on the cancer cell type and the organ. Even when a nutrient was scarce in a tissue, tumors could still grow if they found other ways to adapt, like salvaging nutrients from surrounding cells. One major finding is that purine synthesis is a universal requirement for metastasis in breast cancer, regardless of the nutrient environment.

Q: What are the implications?

This study shows that cancer’s ability to spread isn’t dictated by a single missing nutrient but instead by a complex mix of cell-intrinsic traits and the local environment. Our results challenge the idea that targeting a single nutrient pathway will stop metastasis. Instead, we need to think more holistically, considering combinations of nutrient availability, genetic vulnerabilities, and interactions with surrounding cells.

By identifying purine synthesis as a consistent vulnerability, this research also points to potential therapeutic targets that might help prevent or treat metastases more broadly across different tissues.

Q: What are the next steps?

Future work will explore how other cancer types respond to nutrient deprivation and whether combinations of therapies, including metabolic inhibitors, could selectively block tumor growth in specific organs. We also want to better understand how cancer cells adapt to nutrient-limited environments using strategies like nutrient scavenging or support from nearby cells.

Long term, we hope this kind of work will help personalize cancer therapy based on where tumors are likely to spread and how they feed themselves once they arrive.