Reprogramming strategies for the establishment of novel human cancer models.
Cancer comprises heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. The emergence of the "cancer stem cell" (CSC) hypothesis that they are the cells responsible for resistance, metastasis and secondary tumor appearance identifies these populations as novel obligatory targets for the treatment of cancer. CSCs, like their normal tissue-specific stem cell counterparts, are multipotent, partially differentiated, self-sustaining, yet transformed cells. To date, most studies on CSC biology have relied on the use of murine models and primary human material. In spite of much progress, the use of primary material presents several limitations that limit our understanding of the mechanisms underlying CSC formation, the similarities between normal stem cells and CSCs and ultimately, the possibility for developing targeted therapies. Recently, different strategies for controlling cell fate have been applied to the modeling of human cancer initiation and for the generation of human CSC models. Here we will summarize recent developments in the establishment and application of reprogramming strategies for the modeling of human cancer initiation and CSC formation.
a Institute of Hepatology, Foundation for Liver Research , London , UK.|b Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital , London , UK.
Ignacio
I
Sancho-Martinez
c Gene Expression Laboratory Belmonte, Salk Institute for Biological Studies , La Jolla , CA , USA.
Juan Carlos
JC
Izpisua Belmonte
D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D065150:Cellular Reprogramming; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*
cancer stem cells; driver mutations; iPSCs; reprogramming; transformation