A recent study published in Nature Communications on September 28, 2024, led by Daniele Gilkes, Ph.D., at Johns Hopkins Kimmel Cancer Center, has identified 16 genes that enable breast cancer cells to survive in the bloodstream after escaping low-oxygen tumor regions.

These genes help cancer cells withstand reactive oxygen species, a lethal stress encountered during their migration to the bloodstream, thereby increasing their survival odds post-tumor removal.

The findings are particularly relevant for triple-negative breast cancer (TNBC), which is known for its high recurrence rates; biopsies from patients with recurrent TNBC showed elevated levels of the protein MUC1.

Gilkes' team demonstrated that blocking MUC1 with the compound GO-203 reduced the ability of hypoxic breast cancer cells to survive in the bloodstream and decreased metastasis in mouse models.

A phase I/II clinical trial targeting MUC1 in patients with advanced cancers, including breast and ovarian cancers, is currently underway, indicating its potential for broader application across various solid tumor types.

The study utilized spatial transcriptomics to analyze hypoxic cells in mice, revealing that certain genes remain active even after cancer cells migrate to more oxygenated environments.

The research indicates that cells exposed to chronic hypoxia can retain a 'memory' of these conditions, allowing them to continue expressing hypoxia-induced genes even after returning to normal oxygen levels.

Lower oxygen levels in tumors correlate with worse patient prognosis, as these cells are more adept at surviving systemic circulation.

The study emphasizes the need for further research to understand the broader implications of these findings across different cancer types.

The research was supported by multiple organizations, including The Jayne Koskinas Ted Giovanis Foundation for Health and Policy and the National Cancer Institute, with contributions from various co-authors affiliated with Johns Hopkins and the NIH.

Lead author Daniele Gilkes explains that cancer cells in hypoxic environments migrate to oxygen-rich blood, which increases their chances of metastasis.

Overall, this study highlights the potential of these identified genes as therapeutic targets to prevent cancer recurrence, with MUC1 already undergoing clinical trials.