Aspirin suppresses the acquisition of chemo-resistance in breast cancer by disrupting an NF{kappa}B-IL6 signaling axis responsible for the generation of cancer stem cells

Acquired chemo-resistance has curtailed cancer survival since the dawn of the chemotherapy. Accumulating evidence suggests a major role for cancer stem cells (CSCs) in chemo-resistance, though their involvement in acquired resistance is still unknown. The use of aspirin has been associated with reduced cancer risk and recurrence, suggesting that the anti-inflammatory drug may exert effects on CSCs. In this study, we investigated the contribution of CSCs to acquired chemo-resistance of breast cancer and the avenues for reversing such effects with aspirin. We observed that the residual risk of recurrence was higher in breast cancer patients who had acquired chemo-resistance. Treatment of pre-existing CSCs with a genotoxic drug combination (5-fluorouracil, adriamycin, and cyclophosphamide) generated an NFκB-IL6-dependent inflammatory environment that imparted stemness to non-stem cancer cells, induced multi-drug resistance, and enhanced the migration potential of CSCs. Treatment with aspirin prior to chemotherapy suppressed the acquisition of chemo-resistance by perturbing the nuclear translocation of NFκB in pre-existing CSCs. Therefore, disruptions to the NFκB-IL6 feedback loop prevented CSC induction and sensitized pre-existing CSCs to chemotherapy. Collectively, our findings suggest that combining aspirin and conventional chemotherapy may offer a new treatment strategy to improve recurrence-free survival of breast cancer patients.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfqXgb
via IFTTT