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This Week in Cancer Discovery: May 30, 2012

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In Cancer Discovery, researchers in the US and Australia report that pre-existing MEK1 exon 3 mutations in V600E/KBRAF melanomas don't confer resistance to BRAF inhibitors. The team sequenced MEK1/2 exon 3 in 31 melanomas at disease diagnosis and at progression, and found that five of them carried concurrent somatic BRAF/MEK1 activating mutations. Three of those five patients showed objective responses to BRAF inhibitors, consistent with the overall response rate to these drugs. "MEK1-mutant expression in V600E/KBRAF melanoma cell lines resulted in no significant alterations in p-ERK1/2 levels or growth-inhibitory sensitivities to BRAFi, MEK1/2 inhibitor, or their combination," the authors write. "Thus, activating MEK1 exon 3 mutations identified herein and concurrent with V600E/KBRAF do not cause BRAF [inhibitor] resistance in melanoma."

Also in Cancer Discovery, researchers at Harvard Medical School and Dana-Farber Cancer Institute present their functional characterization of an isoform-selective inhibitor of PI3K-p110β. The team used a panel of PI3K isoform-specific cellular assays to screen compounds that act against kinases in the PI3K superfamily. They identified a selective p110β inhibitor called KIN-193, which they say is "efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110β activation or PTEN loss." When the drug was profiled across a panel of 422 human tumor cell lines, the team found that the cancer cells' PTEN mutation status strongly correlated with their response to KIN-193. "Together, our data provide the first pharmacologic evidence that PTEN-deficient tumors are dependent on p110β in animals and suggest that KIN-193 can be pursued as a drug to treat tumors that are dependent on p110β while sparing other PI3K isoforms," they add.

The Scan

Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

Time to traditional approval or withdrawal was shorter when confirmatory trials started prior to accelerated approval, though overall regulatory outcomes remained similar, a JAMA study finds.

Sequencing Study Leads to Vaccine Target in Bacteria Behind Neonatal Meningitis

Researchers eBioMedicine track down potential vaccine targets with transposon sequencing on mutant bacteria causing neonatal meningitis in mouse models of the disease.

Multiple Myeloma Progression Influenced by Immune Microenvironment Expression

Researchers in NPJ Genomic Medicine compare RNA sequencing profiles of 102,207 individual cells in bone marrow samples from 18 individuals with rapid or non-progressing multiple myeloma.

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.