In 2007, the CSC hypothesis was thrown for a loop, however, after a team led by Kornelia Polyak, of the Harvard Medical School and Dana-Farber Cancer Institute in Boston, probed a bit deeper into the Michigan team's findings. In this month's Hot Paper, [reference 2] Polyak's team compared the genetic profiles of the putative breast CSCs with other more differentiated cells, and found several genetic differences between the two cell populations. This "raises doubts about whether they are direct descendents of one another," says Polyak.
Notably, Baylor oncologist Jenny Chang, together with her colleague Jeffrey Rosen, compared breast tumors in patients before and after chemotherapy, and found a three-fold enrichment in cells resembling CSCs following treatment, signifying that tumorigenic cells are, indeed, more resilient. [reference 5] "There are different subpopulations of [cancer] cells that we need to target separately," says Chang. These results lend credibility to the CSC hypothesis where it really counts, adds Wicha. "It's a valid model because it actually predicts behavior in the clinic," he says.Reference 2: M. Shipitsin et al., "Molecular definition of breast tumor heterogeneity," Cancer Cell, 11:259-73, 2007. [PubMed Citation].
Reference 5: X. Li et al., "Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy," J Natl Cancer Inst, 100:672-9, 2008. [PubMed Citation].