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This Week in the Journal of the National Cancer Institute: Mar 22, 2012


This week in the Journal of the National Cancer Institute, an international team of researchers reports on the CYP2D6 genotype and its effect on tamoxifen response in postmenopausal women with endocrine-responsive breast cancer. The researchers analyzed the DNA of 4,861 postmenopausal women with hormone receptor-positive breast cancer and genotyped it for nine CYP2D6 SNPs. They found no associations between CYP2D6 metabolism phenotypes and breast cancer-free interval in patients taking tamoxifen alone. They did find, however, that CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flashes. "CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes, contrary to the hypothesis," the team writes. "The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen."

Also in the Journal of the National Cancer Institute this week, researchers in the US and Finland examine the effects of Ang2 inhibitors on lung metastasis. The team created a mouse model of tumor-bearing immunodeficient mice over-expressing Ang2, and then administered Ang2-blocking antibodies to the mice. They found that adenoviral expression of Ang2 led to increases in lymph node and lung metastasis in the tumor xenografts. "The metastatic burden in the lungs was increased in transgenic mice in which Ang2 expression was induced specifically in the vascular endothelium," the authors write. "Ang2-blocking antibodies reduced lymph node and lung metastasis, as well as tumor lymphangiogenesis, and decreased tumor cell homing to the lungs after intravenous injection."

Finally in the Journal of the National Cancer Institute this week, researchers at the University of North Carolina, Chapel Hill, report on the use of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. "We believe that the present data support a possible role for CDK4/6 inhibitors in a majority of patients with advanced cancer: to either inhibit tumor growth in CDK4/6-dependent tumors or ameliorate the dose-limiting toxicities of chemotherapy in CDK4/6-indepdendent tumors," the authors write. "Our data also suggest CDK4/6 inhibitors should not be combined with DNA-damaging therapies, such as carboplatin, to treat tumors that require CDK4/6 activity for proliferation."

The Scan

Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

Researchers in Nature Genetics detect somatic mutation variation across iPSCs generated from blood or skin fibroblast cell sources, along with selection for BCOR gene mutations.

Researchers Reprogram Plant Roots With Synthetic Genetic Circuit Strategy

Root gene expression was altered with the help of genetic circuits built around a series of synthetic transcriptional regulators in the Nicotiana benthamiana plant in a Science paper.

Infectious Disease Tracking Study Compares Genome Sequencing Approaches

Researchers in BMC Genomics see advantages for capture-based Illumina sequencing and amplicon-based sequencing on the Nanopore instrument, depending on the situation or samples available.

LINE-1 Linked to Premature Aging Conditions

Researchers report in Science Translational Medicine that the accumulation of LINE-1 RNA contributes to premature aging conditions and that symptoms can be improved by targeting them.