Research News

Cleveland Clinic has found an interesting link between cancer metabolism, the tumor microbiome and breast cancer survival. The Scientific Reports study shows that the bacteria Staphylococcus aureus (“staph”) can sensitize treatment-resistant breast cancer to therapy by recruiting immune cells and blocking cancer metabolism. These findings point to new metabolic biomarkers and potential therapies for cancer targeting the tumor microbiome.

The work began in the laboratory of the late Charis Eng, MD, PhD, and continued in the laboratory of Ying Ni, PhD.

Previous studies had shown that women with breast cancer were less likely to survive if they took antibiotics before their cancer treatment. Dr. Eng and her team, including first author Chin-Chih (Gin) Liu, PhD, wondered if the antibiotics were killing helpful bacteria in the tumor microbiome. By analyzing bacteria living in the tumors of 46 women receiving breast cancer treatment, they found that higher levels of staph were associated with greater immune activity inside breast tumors. This immune activity may enhance anti-tumor immune responses in treatment-resistant triple-negative breast cancer.

Staph can cause infections under certain circumstances, but noninfectious strains are part of a healthy skin microbiome. Dr. Eng’s early findings suggested it might be part of a healthy tumor microbiome, as well.

Drs. Ni and Liu also looked at whether the bacteria could somehow be impacting the cancer cells’ metabolism. “Bacteria in the gut microbiome play a critical role in regulating metabolism across our whole bodies, so it stands to reason that bacteria in a tumor microbiome could have a more local effect,” she says.

What is cancer metabolism?

Cancer metabolism refers to the unique biological ways cancer cells make and expend energy. One of the first things mutated cells do to become cancerous is to reprogram their metabolism, ensuring the energy the cancer cells need to grow and divide as quickly as possible. Noncancerous cells in our bodies also change to promote cancer metabolism, forming a dynamic community where cancer cells, surrounding immune cells, surrounding healthy tissue and even bacteria inside a tumor exchange nutrients and signals.

Dr. Ni says that understanding these metabolic interactions helps researchers identify vulnerable pathways that could be disrupted to slow growth or restore the body’s natural immune defenses.

Cancer metabolism is an attractive drug target because it’s so critical to the disease’s survival. A drug that can reliably block or slow a tumor’s metabolism could potentially slow or destroy the cancer with minimal side effects in healthy cells. This is especially attractive for difficult-to-treat cancers like triple-negative breast cancer, a focus of this paper.

Staphylococcus remodels the tumor metabolic environment and activates immune cells

In preclinical models, bacteria-free tumors injected with staph were easier to treat, even if the tumor was otherwise treatment-resistant. They also had changes in their metabolic pathways, reducing NAD—a critical molecule that helps cells make energy.

In biopsy samples from another cohort of women receiving treatment, tumors with higher levels of staph had more cancer-fighting immune cells inside and produced less NAD. Together, these findings suggest that bacteria within the tumor microbiome may help reshape the metabolic microenvironment in ways that support the immune system's ability to recognize and attack cancer.

“We aren’t sure exactly how bacteria get into a breast cancer tumor, but if even a few make it in, we see a very strong impact,” Dr. Ni says. “This study shows that tumors are not just collections of cancer cells—they are complex ecosystems where bacteria, immune cells and metabolism continuously interact. Whether we target the microbiome itself or the molecules it affects, the future looks promising.”