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This Week in Cancer Research: Apr 6, 2012

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In Cancer Research this week, researchers at the University of Michigan explore PARP-1 inhibition as a targeted treatment for Ewing's sarcoma. The team found that the products of gene fusions that characterize Ewing's sarcoma interact with PARP-1, and that the sarcoma's cells are sensitive to PARP-1 inhibition. "Addition of a PARP1 inhibitor to the second-line chemotherapeutic agent temozolamide resulted in complete responses of all treated tumors in an EWS-FLI1–driven mouse xenograft model of [Ewing's sarcoma]," the authors write." Mechanistic investigations revealed that DNA damage induced by expression of EWS-FLI1 or EWS-ERG fusion genes was potentiated by PARP1 inhibition in ESFT cell lines."

Also in Cancer Research this week, researchers in Japan report the tumor cell–derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis. In mice, ANGPTL2 has been implicated in inflammatory carcinogenesis, and elevated levels of ANGPTL2 in patients with lung cancer are associated with reduction in disease-free survival after surgical resection, the team writes. "Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased ANGPTL2 expression," the researchers add. "Most notably, tumor cell–derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype." These findings suggest that ANGPTL2 drives metastasis, and inhibiting it could inhibit the metastatic process, they write.

Finally in Cancer Research this week, researchers in the US and Greece report an association between resistance to rapamycin and defective regulation of Skp2, a subunit of the ubiquitin protein ligase complex. "The ability of rapamycin to downregulate Skp2 … identifies tumors that are sensitive to rapamycin," the authors write. "RNA interference–mediated silencing of Skp2 in human tumor cells increased their sensitivity to rapamycin in vitro and inhibited the growth of tumor xenografts in vivo." These findings suggest that Skp2 levels are important in determining response to mTOR inhibitors like rapamycin, which could be an important pharmacogenomic marker, they add.

The Scan

And For Adolescents

The US Food and Drug Administration has authorized the Pfizer-BioNTech SARS-CoV-2 vaccine for children between the ages of 12 and 15 years old.

Also of Concern to WHO

The Wall Street Journal reports that the World Health Organization has classified the SARS-CoV-2 variant B.1.617 as a "variant of concern."

Test for Them All

The New York Times reports on the development of combined tests for SARS-CoV-2 and other viruses like influenza.

PNAS Papers on Oral Microbiome Evolution, Snake Toxins, Transcription Factor Binding

In PNAS this week: evolution of oral microbiomes among hominids, comparative genomic analysis of snake toxins, and more.