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This Week in Cancer Discovery: Apr 20, 2012


In Cancer Discovery this week, researchers in the UK and Switzerland report they performed a functional metabolic screen to identify the gene PFKFB4 as an important regulator of prostate cancer cell survival. The team analyzed the effect of silencing 222 different enzymes, transporters, and regulators on the survival of three metastatic prostate cancer cell lines and one non-malignant prostate cancer cell line and found that there are several genes required for the cells' survival. Among them was PFKFB4, which is required to "balance glycolytic activity and antioxidant production to maintain cellular redox balance in prostate cancer cells," the team writes. When the researchers depleted the gene in a xenograft model of prostate cancer, tumor growth was inhibited. "PFKFB4 mRNA expression was also found to be greater in metastatic prostate cancer compared with primary tumors," they add. "Taken together, these results indicate that PFKFB4 is a potential target for the development of antineoplastic agents."

Also in Cancer Discovery this week, researchers at the Institute of Cancer Research in the UK report that treatment of BRAFV600E-driven melanoma with metformin accelerates the cancer's growth through the up-regulation of VEGF-A. The team says that melanoma cells driven by oncogenic BRAF are resistant to the effects of metformin — which has been shown to inhibit tumor growth in a variety of cancers by inhibiting TORC1 — because TORC1 activity is sustained by the signal transducer RSK. Further, the team says, VEGF-A is also up-regulated, which drives angiogenesis and accelerates tumor growth. When VEGF signaling is inhibited, the researchers add, metformin inhibits tumor growth in mice. "VEGF inhibitors and metformin synergize to suppress the growth of BRAF-mutant tumors, revealing a combination of drugs that may be effective in these patients," they write.

Finally in Cancer Discovery this week, researchers in the US and Denmark report that allelic imbalance in the telomeres of cancer patients indicate they may be sensitive to DNA-damaging agents. The team analyzed various cancer cell lines and tumors to find genomic signatures of defective DNA repair. They found that the number of sub-chromosomal regions with allelic imbalance all the way to the telomere was predictive of cisplatin sensitivity in vitro in patients with triple-negative breast cancer. Further, in patients with serous ovarian cancer, higher levels of telomeric allelic imbalance predicted a better response to treatment with platinum-based chemotherapy, they add. "Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations also benefit from these agents," the team writes. "[The number of sub-chromosomal regions with allelic imbalance extending to the telomere], a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair."

The Scan

Comfort of Home

The Guardian reports that AstraZeneca is to run more clinical trials from people's homes with the aim of increasing participant diversity.

Keep Under Control

Genetic technologies are among the tools suggested to manage invasive species and feral animals in Australia, Newsweek says.

Just Make It

The New York Times writes that there is increased interest in applying gene synthesis to even more applications.

Nucleic Acids Research Papers on OncoDB, mBodyMap, Genomicus

In Nucleic Acids Research this week: database to analyze large cancer datasets, human body microbe database, and more.