A new study has identified the protein SLC5A11 as the key reason the diabetes drug metformin can also work as a cancer treatment. Researchers used a genome-wide CRISPR screen and found that metformin must bind to SLC5A11 to trigger its anti-cancer effects. Without this protein, the drug loses its ability to work against tumors.
The study shows that metformin activates a chain reaction inside cancer cells that ultimately reduces PD-L1, a molecule tumors use to hide from the immune system. By lowering PD-L1, cancer cells become more visible to immune attack.
In preclinical models, combining metformin with anti-PD-1 immunotherapy led to strong tumor shrinkage, especially in hard-to-treat cancers like pancreatic cancer. In lung cancer models, the combination improved survival, while all untreated animals died within a month. It also increased the presence of cancer-fighting T cells inside tumors.
Because metformin is already widely used and inexpensive, researchers believe this discovery could help improve immunotherapy outcomes across several cancer types, pending further clinical studies.