factor Hes3 regulates a number of cultured cells with CSC characteristics obtained from glioblastoma patients. Sonic hedgehog and Wnt These developmental pathways are SC regulators. Both Sonic hedgehog (SHH) and Wnt pathways are commonly hyperactivated in tumors and are necessary to sustain tumor growth. However, the Gli transcription factors that are regulated by SHH take their name from gliomas, where they are highly expressed. A degree of crosstalk exists between the two pathways and they are commonly activated together. By contrast, in colon cancer hedgehog signalling appears to antagonise Wnt. Sonic hedgehog blockers are available, such as cyclopamine. A water-soluble cyclopamine may be more effective in cancer treatment. DMAPT, a water-soluble derivative of parthenolide, induces oxidative stress and inhibits NF-κB signaling for AML (leukemia) and possibly myeloma and prostate cancer. Telomerase is a study subject in CSC physiology. GRN163L (Imetelstat) was recently started in trials to target myeloma stem cells. Wnt signaling can become independent of regular stimuli, through mutations in downstream oncogenes and tumor suppressor genes that become permanently activated even though the normal receptor has not received a signal. β-catenin binds to transcription factors such as the protein TCF4 and in combination the molecules activate the necessary genes. LF3 strongly inhibits this binding in vitro, in cell lines and reduced tumor growth in mouse models. It prevented replication and reduced their ability to migrate, all without affecting healthy cells. No cancer stem cells remained after treatment. The discovery was the product of "rational drug design", involving AlphaScreens and ELISA technologies. References Further reading Stem cells Carcinogenesis