The factors that determine where in the body breast cancer can metastasize are not well understood. It is likely, however, that the metabolic profile of any given tissue plays a role. Researchers led by Ludwig Harvard’s Rakesh Jain and Ludwig MIT’s Matthew Vander Heiden and their Harvard colleague George Church reported in a January issue of Nature their findings from a sweeping examination in mice of the metabolic conditions that make tissues amenable to breast cancer metastasis. The researchers quantified the absolute levels of 124 nutrients in various mouse tissues to chart the metabolic landscape encountered by metastasizing cells. They then examined how this relates to the ability of tissues to host breast cancer metastases by engineering breast cancer cells to disrupt their synthesis of specific nutrients and testing their ability to grow in those tissues. They found that no single nutrient accounts for such ability in any tissue. Rather, it is the interplay of intrinsic cancer cell traits and multiple nutrients in the tissue microenvironment that determines whether a breast cancer cell can seed a metastatic tumor. However, purine synthesis did emerge as an indispensable requirement for breast cancer metastasis and tumor growth across multiple tissues. That dependency was unaltered by the availability of nucleotides in any given tissue or their synthesis by tumor cells. This finding suggests a general terrain for the discovery of therapeutic targets.
Nutrient requirements of organ-specific metastasis in breast cancer
Nature, 2026 January 7