distinguish CSCs from others. In 2009, scientists identified the compound salinomycin, which selectively reduces the proportion of breast CSCs in mice by more than 100-fold relative to Paclitaxel, a commonly used chemotherapeutic agent. Some types of cancer cells can survive treatment with salinomycin through autophagy, whereby cells use acidic organelles such as lysosomes to degrade and recycle certain types of proteins. The use of autophagy inhibitors can kill cancer stem cells that survive by autophagy. The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in acute myelogenous leukemia (AML) but not on normal CD34+CD38- bone marrow cells. Treating AML-engrafted NOD/SCID mice with a CD123-specific monoclonal antibody impaired LSCs homing to the bone marrow and reduced overall AML cell repopulation including the proportion of LSCs in secondary mouse recipients. A 2015 study packaged nanoparticles with miR-34a and ammonium bicarbonate and delivered them to prostate CSCs in a mouse model. Then they irradiated the area with near-infrared laser light. This caused the nanoparticles to swell three times or more in size bursting the endosomes and dispersing the RNA in the cell. miR-34a can lower the levels of CD44. A 2018 study identified inhibitors of the ALDH1A family of enzymes and showed that they could selectively deplete putative cancer stem cells in several ovarian cancer cell lines. Pathways The design of new drugs for targeting CSCs requires understanding the cellular mechanisms that regulate cell proliferation. The first advances in this area were made with hematopoietic stem cells (HSCs) and their transformed counterparts in leukemia, the disease for which the origin of CSCs is best understood. Stem cells of many organs share the same cellular pathways as leukemia-derived HSCs. A normal stem cell may be transformed into a CSC through dysregulation of the proliferation and differentiation pathways controlling it or by inducing oncoprotein activity. BMI-1 The Polycomb group transcriptional repressor Bmi-1 was discovered as a common oncogene activated in lymphoma and later shown to regulate HSCs. The role of Bmi-1 has been illustrated in neural stem cells. The pathway appears to be active in CSCs of pediatric brain tumors. Notch The Notch pathway plays a role in controlling stem cell proliferation for several cell types including hematopoietic, neural and mammary SCs. Components of this pathway have been proposed to act as oncogenes in mammary and other tumors. A branch of the Notch signaling pathway that involves the transcription