癌症研究进展课件.pdf

Cell-of-origin and cancer stem cell Cell-of-origin and cancer stem-cell are distinct CSC: Cancer Stem Cell Visvader (2011) Nature 469:314 Cancer stem cell Nature Medicine (2011) 17: 313 Nature Medicine (2011) 17: 313 Cancer stem cell (CSC) Not all cells in a tumor are equal (postmitotic cells, differentiated cells and rapid proliferating cells). CSCCSC expllaiins poorlly unddersttoodd cliliniicall phhenomena 1.Renew themselves 2.Last lifelong 3.Resistant to eletromagnetic and chemical insults 4.Dormant 5.Colonize other body parts 6.Initial response to therapy doesn’t mean cure. IfIf CSCCSC conceptt iis correctt, ththe aiim off ththerapy should not be targeting the tumor bulk, but kill the “beating heart”. History of CSC concept 1937, Further and Kahn observed a single cell from a mouse tumor could grow new tumor. 1964, Piece showed that tumor cells could differentiate into multiplemultiple differentiateddifferentiated, nontumorigenicnontumorigenic cellscells. Mid-1900, pproliferatingg cells can be radiolabeled 1971, Piece showed early labeling occurred almost all in the undifferentiatedundifferentiated areasareas. 19970s,0s, ddiscoscoveereded muutaatioonss in ooncogecogeneses aandd tuumoor suppressor genes. 1976, Nowell formulated “clonal evolution concept”. Clonal evolution concept Cancer arise from a single cell of origin, and acquired genetic variability within the original clone to form more aggressive sublines. • ThiThis suggestts ththatt eachh person’’s cancer may require individual specific therapy • Even this may be thwarted by emergence of a geneticallygenetically variantvariant sublinesubline resistantresistant toto thethe treatmenttreatment Revival of the CSC concept Techno