In a Cell paper published online in advance, MIT's Angelika Amon and her colleagues report on their screen of four trisomic mouse embryonic fibroblast lines, in which they found aneuploidy-selective anti-proliferation compounds. Amon et al. add that "AICAR and 17-AAG, especially when combined, also show efficacy against aneuploid human cancer cell lines." The team suggests that anti-proliferation compounds, such as those that "interfere with pathways that are essential for the survival of aneuploid cells," point to a potential "new treatment strategy against a broad spectrum of human tumors."
Over in Cancer Cell this week, a collaborative team led by investigators at the Taussig Cancer Center and Lerner Research Institute in Cleveland, Ohio, and researchers at the University of Texas Health Science Center, San Antonio, show using "Ptch1, p53, and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin" that loss of Rb1 is an "apparent modifier for sarcomas by inducing de-differentiation." Overall, the team says that "sarcoma phenotype is strongly influenced by cell of origin and mutational profile."
Investigators at the Netherlands Cancer Institute describe "a functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer." In a paper published online this week in Cancer Cell, the team shows that as small cell lung cancer "tumors are often composed of phenotypically different cells with either a neuroendocrine or a mesenchymal marker profile," crosstalk between them, and tumor cell heterogeneity overall, may play a significant role in dictating tumor properties.
Tufts University's Charlotte Kuperwasser et al. show in Cell Stem Cell this week that "genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate." More specifically, Kuperwasser and her colleagues characterized breast epithelial cells derived from patients with deleterious BRCA1 mutations and show that they "give rise to tumors with increased basal differentiation relative to cells from BRCA1+/+ patients." Further, the team reports that Slug, which is "aberrantly expressed in BRCA1mut/+ tissues," represses human breast progenitor cell lineage commitment and differentiation; expression of Slug, the group adds, is "necessary for increased basal-like phenotypes prior to and after neoplastic transformation."