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This Week in Cancer Discovery: Aug 18, 2011

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Researchers from the Institute of Cancer Research in London report in Cancer Discovery that functional genetic profiling of breast cancer allows the cancer to be classified into subgroups that are different from established subtypes. Using an siRNA library targeting human protein kinases in breast tumor cell lines, the researchers confirm that ERBB2 and PIK3CA are candidate targets for breast cancer therapeutics. "We describe how functional viability profiles of breast tumor cell lines may be used to identify novel candidate therapeutic targets, as well as increasing our understanding of the fundamental dependencies that breast tumor cells carry," the researchers write. As far as we are aware, this is the first attempt to comprehensively identify genetic dependencies for a set of potentially druggable genes in breast cancer cell lines.

Dana-Farber Cancer Institute's William Kaelin and his colleagues found that HIF1α is the target of chromosome 14q deletion in kidney cancer. "Wild-type HIF1α suppresses renal carcinoma growth, but the products of these altered loci do not. Conversely, downregulation of HIF1α in HIF1α-proficient lines promotes tumor growth," the authors write. They add that HIF1α appears to be a kidney cancer suppressor gene.

Massachusetts General Hospital's Jeffrey Engelman and his team report in Cancer Discovery on how cancer cell lines driven by the same oncogenes respond to selective kinase inhibitors. The group reports that there was a range of cell death due to the kinase inhibitor and that "pre-treatment RNA levels of the BH3-only pro-apoptotic BIM strongly predicted the capacity of EGFR, HER2, and PI3K inhibitors to induce apoptosis in EGFR mutant, HER2 amplified, and PIK3CA mutant cancers, respectively, but BIM levels did not predict responsiveness to standard chemotherapies," it adds.

The Scan

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.

Study Explores Animated Digital Message Approach to Communicate Genetic Test Results to Family Members

In the Journal of Genetic Counseling, the approach showed promise in participants presented with a hypothetical scenario related to a familial hereditary breast and ovarian cancer syndrome diagnosis.

Computational Tool Predicts Mammalian Messenger RNA Degradation Rates

A tool called Saluki, trained with mouse and human messenger RNA data, appears to improve mRNA half-life predictions by taking RNA and genetic features into account, a Genome Biology paper reports.

UK Pilot Study Suggests Digital Pathway May Expand BRCA Testing in Breast Cancer

A randomized pilot study in the Journal of Medical Genetics points to similar outcomes for breast cancer patients receiving germline BRCA testing through fully digital or partially digital testing pathways.