Abstract BS3-2: Targeting mitochrondria with FDA-approved antibiotics may be a new therapeutic strategy to eliminate cancer stem cells

Our recent studies indicate that cancer stem cells (CSCs) have increased mitochondrial mass, which directly reflects an increase in mitochondrial biogenesis and OXPHOS capacity. Thus, we believe that more effective anti-cancer therapy would involve the strategic targeting of CSC mitochondria, to prevent or reverse tumor recurrence, metastasis and drug-resistance. Interestingly, mitochondria are originally derived from aerobic bacteria that were engulfed by eukaryotic cells and adapted over millions of years of evolution. This is known as the 'Endo-symbiotic Theory of Mitochondrial Evolution'. As a consequence, certain antibiotics target mitochondrial protein translation as a manageable side effect. We have recently proposed to harness this side effect and to re-purpose it as a therapeutic effect to target breast CSCs. In accordance with this strategy, we have already experimentally identified 4 to 5 different class of mitochondrial-targeted antibiotics that could be used halt the proliferation and eradicate breast CSCs. These antibiotics included azithromycin and doxycycline, among others. Importantly, these antibiotics showed anti-CSC activity in 12 different cell lines, across 8 different cancer types, that were originally derived from breast, DCIS, ovarian, prostate, pancreatic and lung carcinomas, as well as glioblastoma and melanoma. In this context, doxycycline appeared to be one of the most promising agents, as human clinical trials in MALT lymphoma have already shown ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Invited Speaker Abstracts Source Type: research