American Association for Cancer Research

May 1 Cancer Research Highlights

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Selected Articles from the May 1, 2009 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the May 1 issue of Cancer Research.


Global Histone Modifications in Breast Cancer

Elsheikh et al.

Page 3802

Changes in global histone modification patterns have been shown to be predictive of clinical outcome for a variety of cancers, including prostate, lung, and gastric cancers. Elsheikh and colleagues assessed the significance of a select set of histone modifications in a large series of invasive primary breast carcinoma cases. The authors identified variations in histone modifications in different grades, morphologic types, and phenotype classes of invasive breast tumors. Hypomodified and hypermodified tumor clusters that correlate with known prognostic factors and clinical outcome were also identified. This study identifies the presence of variations in global levels of histone modifications and shows that these differences have clinical significance in breast cancer. 
 

Bladder Cancer Multiplex Quantitative PCR Signature

Wang et al.

Page 3810

Wang et al.There is currently no reliable method for predicting bladder cancer progression to muscle-invasive disease. Wang and colleagues have developed a clinically applicable quantitative polymerase chain reaction gene signature to predict likelihood for progression in bladder cancer. This signature was derived from the most robust genes identified from previously published DNA microarray studies and, when applied to 96 non–muscle-invasive bladder tumors, provided predictive improvement for progression over clinical stage and gender. This study provides a framework for converting microarray data into a cancer multiplex assay that may help further guide clinical management.


PARP-1 Inhibitor Treatment of Brca2/p53-Mutant Tumors

Hay et al.

Page 3850

Novel therapeutic strategies are being developed based on the notion of synthetic lethality. In mammary tumors, this is being pursued through the inhibition of the DNA repair enzyme poly-(ADP-ribose) polymerase-1 (PARP-1) in tumors carrying defects in homologous recombination. Hay and colleagues report the modeling of a potent PARP inhibitor (AZD2281) in autochthonous tumors arising in mice carrying mammary-specific mutations in Brca2 and p53. Daily exposure to AZD2281 led to tumor regression or growth inhibition in 46 out of 52 tumors. The authors also show combined therapy with carboplatin and AZD2281 significantly increased the time to tumor relapse. These results add substantial weight to the concept of PARP inhibition in targeted mammary tumor therapy. 


Okada et al.The NF2 tumor suppressor gene encodes an intracellular membrane-associated protein, merlin, which couples glycoproteins to the actin cytoskeleton. Merlin suppresses PI3K/Akt signaling and, in turn, Akt phosphorylates merlin, triggering its degradation. Okada and colleagues report that merlin associates directly with phosphatidylinositols and that phosphorylation by Akt inhibits its proapoptotic activity and promotes cell migration. This dual regulation provides a novel mechanism explaining how oncogenic PI3K signaling regulates merlin’s tumor suppressive activity via both Akt and phosphatidylinositol lipids.  


Smyd4 Is a Putative Tumor Suppressor

Hu et al.

Page 4067

The five-member Smyd family is involved in breast cancer development and tumorigenesis through their lysine methyltransferase activity for histone and nonhistone proteins. Hu and colleagues found that the disruption of one allele of Smyd4 gene through chromosome rearrangement leads to tumorigenesis of mammary epithelial cells. Re-expression of Smyd4 inhibits tumor development in nude mice. The authors also demonstrate that Smyd4 suppresses the expression of Pdgfr-α. These results, together with the observation that Smyd4 is silenced in a proportion of primary breast cancers, support the idea that Smyd4 functions as a tumor suppressor.  


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