AKT as locus of cancer multidrug resistance and fragility.

Complexity and robustness of cancer hypoxic microenvironment are supported by the robust signaling networks of autocrine and paracrine elements creating powerful interactome for multidrug resistance. These elements generate a positive feedback loops responsible for the extreme robustness and multidrug resistance in solid cancer, leukemia, myeloma, and lymphoma. Phosphorylated AKT is a cancer multidrug resistance locus. Targeting that locus by oxidant/antioxidant balance modulation, positive feedback loops are converted into negative feedback loops, leading to disappearance of multidrug resistance. This is a new principle for targeting cancer multidrug resistance by the locus chemotherapy inducing a phenomenon of loops conversion.