Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease

摘要: Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via selective targeting cancer stem cells (CSCs), a.k.a., tumor-initiating (TICs). We searched global phenotypic characteristic that was highly conserved among cells, across multiple tumor types, to provide mutation-independent approach therapy. This would allow us target effectively treating as single disease "stemness", independently tissue type. Using this approach, identified weak point - strict dependence on mitochondrial biogenesis clonal expansion survival cells. Interestingly, several classes FDA-approved antibiotics inhibit known "side-effect", which could be harnessed instead "therapeutic effect". Based analysis, now show 4-to-5 different drugs can used eradicate in 12 cell lines, 8 types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, glioblastoma (brain)). These five mitochondrially-targeted include: erythromycins, tetracyclines, glycylcyclines, an anti-parasitic drug, chloramphenicol. Functional data are presented one antibiotic each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, well chloramphenicol, proof-of-concept. Importantly, many these non-toxic normal likely reducing side effects anti-cancer Thus, treat like infectious by repurposing therapy, types. should also considered prevention studies, specifically focused recurrence distant metastasis. Finally, recent clinical trials with doxycycline azithromycin (intended cancer-associated infections, but not cells) have already shown positive therapeutic patients, although their ability yet appreciated.