The antitumour action in vivo of doxycycline, an antibiotic that belongs to the family of tetracyclines and mainly used for the treatment of acne, was recently published in the international journal Frontiers in Oncology, paving the way to a possible use of antibiotics in the treatment of breast cancer.
In fact, as well as eradicating bacteria, the antibiotics also have a destructive effect on mitochondria, the “power stations” of cells, which abound in neoplastic stem cells. These cells are responsible for the origins of tumours, local tumour recurrence, resistance to treatment and the dreaded, distant metastases.
The study was carried out by the research group led by Professor Antonio Giuseppe Naccarato(Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa), who is the director of the Section of Pathological Anatomy 1 of the AOUP - Azienda Ospedaliero-Universitaria Pisana, and Dr. Cristian Scatena, an anatomical pathologist and student in the PhD Program in Clinical and Translational Sciences at the University of Pisa, together with researchers from the University of Salford, Manchester, Great Britain and in collaboration with the AOUP Breast Unit and the Pisa Science Foundation non-profit research institute.
The clinical research was carried out on 15 female patients with early breast cancer and after only 14 days of antibiotic treatment, a significant reduction (on average 40%) in the number of neoplastic stem cells was noted.
Researchers from the University of Salford, coordinated by Professor Michael P. Lisanti, had been studying this effect in tumour models ‘in vitro’ for some time recognizing that doxycycline was able to eradicate the neoplastic stem cells in eight different types of tumours including breast cancer.
These in vitro studies laid the basis for the implementation of the first clinical trials of the use of doxycycline in early breast cancer patients destined therefore for surgical treatment. The trial was carried out in the AOUP Breast Unit directed by Professor Manuela Roncella.
In detail, doxycycline was administered to 9 patients (the experimental group) while a further 6 patients were observed as controls; the former were given the antibiotics at a standard daily dose of 200mg for fourteen days prior to surgery; the latter underwent surgery directly.
Various biomarkers (stemness, mitochondria, cell proliferation etc…) were analysed in both groups of the clinical trial, comparing the results before and after the antibiotic treatment both in pre-operative tumour tissue sections and in post-operative specimens. Post-doxycline tumour samples from the experimental group demonstrated a significant decrease in the stemness marker of between 17.65 and 66.67%. Similar results were also obtained with another stemness biomarker.
The results obtained through this pilot study suggest that neoplastic stem cells selectively over-express key mitochondrial-related proteins. This means that if it is possible to inhibit the mitochondrial function, it is therefore possible to eradicate the neoplastic stem cells.
Additional clinical studies with new patients in the following months will be required to further validate these promising results.
The article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2018.00452/full
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