In Nature this week, a team led by researchers at St. Jude Children's Research Hospital report a novel therapy for retinoblastoma. The team performed genomic and epigenetic analyses of retinoblastoma samples, and found that the cancer's genome is stable, though several of its pathways can be deregulated. As the team reports, the only known cancer gene mutated in these tumors is RB1, and that the overall mutational rate is very low. In addition, the team found that proto-oncogene SYK is up-regulated in retinoblastoma, and is required for the tumor cell survival. "Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumor cell death in vitro and in vivo," the authors write. "Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss."
Also in Nature this week, researchers at the University of Leicester in the UK report that the structure of the cancer drug target HDAC3 is bound to a co-repressor and to inositol tetraphosphate. "The enzymatic activity of most class I HDACs requires recruitment into multi-subunit co-repressor complexes, which are in turn recruited to chromatin by repressive transcription factors," the authors write. In this study, they find that HDAC3 is bound with the deacetylase activation domain from the human SMRT co-repressor. This structure reveals that "there is an essential inositol tetraphosphate molecule — d-myo-inositol-(1,4,5,6)-tetrakisphosphate (Ins(1,4,5,6)P4) — acting as an 'intermolecular glue' between the two proteins," the researchers write. "Assembly of the complex is clearly dependent on the Ins(1,4,5,6)P4, which may act as a regulator—potentially explaining why inositol phosphates and their kinases have been found to act as transcriptional regulators."
Nature features a "Frontiers in Biology" supplement this week. It contains reviews of "important developments in biology," such as research into induced pluripotent stem cells, the role of inflammasomes in disease, and the clonal evolution of cancer.
Finally, Nature this week also features an article on various ways researchers are funding their work, including "crowd-funding." Raising money for research directly from the public is getting to be more and more common as conventional funding sources tighten their budgets, says Nature's Jim Giles. The public seems to be responding to such requests, contributing to projects it finds interesting.