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This Week in Cancer Cell: Mar 30, 2012


In Cancer Cell this week, researchers in the US and South Korea report that the ALK gene and the MYCN oncogene collaborate in the pathogenesis of neuroblastoma. The team generated a transgenic zebrafish model of neuroblastoma, and found that co-expression of activated ALK and MYCN triples the disease's penetrance and accelerates tumor onset. "MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells," the team writes. "Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma."

Also in Cancer Cell this week, researchers in the US and Taiwan report an association between the mTOR and Hedgehog pathways in esophageal adenocarcinoma. The TNF-α/mTOR pathway is known to mediate the development of esophageal cancer, the team writes. Aberrant behavior in Gli1, a downstream effector of the Hedgehog pathway, has also been shown to be involved in this disease. For this study, the team found that "an activated mTOR/S6K1 pathway promotes Gli1 transcriptional activity and oncogenic function through S6K1-mediated Gli1 phosphorylation at Ser84, which releases Gli1 from its endogenous inhibitor, SuFu." Further, the team adds, "elimination of S6K1 activation by an mTOR pathway inhibitor enhances the killing effects of the HH pathway inhibitor." This suggests a rationale for combination therapies for esophageal adenocarcinoma that would affect both pathways.

Finally in Cancer Cell this week, researchers in the US and Europe describe the effect of transient low doses of DNA-demethylating agents like decitabine and azacitidine on hematological and epithelial tumor cells. "We show that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses, without causing immediate cytotoxicity, produce an antitumor memory response, including inhibition of subpopulations of cancer stem-like cells," the team writes. "These effects are accompanied by sustained decreases in genome-wide promoter DNA methylation, gene re-expression, and antitumor changes in key cellular regulatory pathways."

The Scan

J&J Booster Support

A US Food and Drug Administration advisory panel has voted to support a booster dose of Johnson & Johnson's SARS-CoV-2 vaccine, according to the Los Angeles Times.

To Keep the Cases Moving

The president of the UK Royal College of Pathologists tells the Financial Times that more investment is needed to tackle a backlog of cases.

NAS Expels Archaeologist

Science reports Luis Jaime Castillo Butters' expulsion is the first of an international member from the US National Academy of Sciences.

PLOS Papers on Angelman Syndrome-Like Cases, Salmonella Paratyphi A, SARS-CoV-2 in Brazil

In PLOS this week: exome sequencing analysis of Angelman syndrome-like cases, genetic epidemiology of Salmonella Paratyphi A, and more.