Doxycycline pre-operatively in early breast cancer

Cancer stem cells (CSCs) selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline, was performed with known biomarkers of “stemness”, mitochondria, cell proliferation, apoptosis, and neo-angiogenesis. For each patient, the analysis was performed both on pre-operative specimens and surgical specimens. Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value = 0.005). Similar results were also obtained with ALDH1, another marker of stemness. Quantitative decreases in CD44 and ALDH1 expression suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies.