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This Week in Cancer Cell: Jul 24, 2012

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In Cancer Cell this week, researchers in Australia, Germany, and the US and their collaborators at Cylene Pharmaceuticals report that the inhibition of RNA polymerase I could be used as a therapeutic strategy to promote the cancer-specific activation of p53. Human cancers commonly feature increased transcription of rDNA by RNA polymerase I. In this study, the team shows that Cylene's small molecule CX-5461 can be used to target rDNA transcription to kill B-lymphoma cells in vivo while leaving wild-type B cells alone. "The therapeutic effect is a consequence of nucleolar disruption and activation of p53-dependent apoptotic signaling," the authors write. "Human leukemia and lymphoma cell lines also show high sensitivity to inhibition of rDNA transcription that is dependent on p53 mutational status."

Also in Cancer Cell this week, Genentech researchers report that proapoptotic activation of death receptor 5 on tumor endothelial cells reduces the tumor's growth by disrupting its vascular network. The team detected DR5 expression within tumors' endothelial cells, but not in normal tissues. They then found that treating tumor-bearing mice with an oligomeric form of Apo2L/TRAIL, a DR5 ligand, induced apoptosis in tumor endothelial cells, collapsing tumor blood vessels and suppressing its growth. "Vascular disruption and antitumor activity required DR5 expression on tumor [endothelial cells] but not malignant cells," the authors write. "These results establish a therapeutic paradigm for proapoptotic receptor agonists as selective tumor vascular disruption agents, providing an alternative, perhaps complementary, strategy to their use as activators of apoptosis in malignant cells."

Finally in Cancer Cell, researchers in New York and California report that Fanconi anemia tumor suppressing genes interact with RAD51 and BRCA 1 and 2 to suppress tumorigenesis through a distinct replication fork protection pathway. They show there is a repair-independent requirement for Fanconi anemia genes like FANCD2, and in BRCA1, to protect stalled replication forks from degradation. "Fork protection is surprisingly rescued in FANCD2-deficient cells by elevated RAD51 levels or stabilized RAD51 filaments," the authors write. "Moreover, FANCD2-mediated fork protection is epistatic with RAD51 functions, revealing an unanticipated fork protection pathway that connects FA genes to RAD51 and the BRCA1/2 breast cancer suppressors."

The Scan

Mosquitos Genetically Modified to Prevent Malaria Spread

A gene drive approach could be used to render mosquitos unable to spread malaria, researchers report in Science Advances.

Gut Microbiomes Allow Bears to Grow to Similar Sizes Despite Differing Diets

Researchers in Scientific Reports find that the makeup of brown bears' gut microbiomes allows them to reach similar sizes even when feasting on different foods.

Finding Safe Harbor in the Human Genome

In Genome Biology, researchers present a new approach to identify genomic safe harbors where transgenes can be expressed without affecting host cell function.

New Data Point to Nuanced Relationship Between Major Depression, Bipolar Disorder

Lund University researchers in JAMA Psychiatry uncover overlapping genetic liabilities for major depression and bipolar disorder.