However, the current attempts to reverse drug resistance by eradicating CSCs directly or slowing CSC growth indirectly have been far from success, including direct inhibition via CSC-dependent signaling (Wnt/β-catenin, Hedgehog, Notch, FAK, PTEN, Nanog, and JAK/STAT, among others) inhibitors, tumor microenvironment modulators, direct eradication via CD44-targeting or CD133-targeting immunotherapy, and differentiation therapy 39-42. The gene discussed is PTEN; the disease is neoplasm.