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This Week in Cancer Discovery: Mar 23, 2012


In Cancer Discovery this week, researchers in the UK and the Netherlands report that nanoparticle albumin-bound-paclitaxel potentiates gemcitabine activity in a mouse model of pancreatic cancer. Using their model, the researchers show that treatment of pancreatic cancer with a combination of nab-paclitaxel and gemcitabine "uniquely demonstrates evidence of tumor regression." Paclitaxel reduced the levels of the primary gemcitabine metabolizing enzyme, cytidine deaminase, in cultured cells, resulting in an increased stabilization of gemcitabine in those cells, the team found. "Our findings support the concept that suboptimal intratumoral concentrations of gemcitabine represent a crucial mechanism of therapeutic resistance in [pancreatic ductal adenocarcinomas] and highlight the advantages of genetically engineered mouse models in preclinical therapeutic trials," they add.

Also in Cancer Discovery this week, researchers in the US and Europe describe their study of MYC activation in prostate cancer. Over-expression of ubiquitin-specific protease 2a down-regulates a set of microRNAs that collectively increase MYC levels. "By establishing MYC as a target of miR-34b/c, we demonstrate that this cluster functions as a tumor suppressor in prostate cancer cells. We identify a distinct mRNA signature that is enriched for MYC-regulated transcripts and transcription factor binding sites in USP2a overexpressing prostate cancer cells," the authors write. "We demonstrate that these genes are associated with an invasive phenotype in human prostate cancer and that the proliferative and invasive properties of USP2a overexpressing cells are MYC-dependent."

Finally in Cancer Discovery this week, researchers in California say tumor invasion and metastasis in pancreatic neuroendocrine tumors can be suppressed by concurrent inhibition of c-Met and VEGF. The team treated pancreatic neuroendocrine tumors in mice with a neutralizing anti-VEGF antibody, and found that it reduced the tumor burden, but increased tumor hypoxia, hypoxia-inducible factor-1α, and c-Met activation, which in turn increased invasion and metastasis. However, the team also found that adding a c-Met inhibitor concurrent to the VEGF inhibitor reduced invasion and metastasis. "These findings document that invasion and metastasis are promoted by selective inhibition of VEGF signaling and can be reduced by the concurrent inhibition of c-Met," they write.

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.