21.05.2013 - Dutch cancer experts have found an enzyme that seems to induce cancer senescence.
When oncogenes are activated inside a cell, they normally mobilise tumour suppressor networks which can act like a brake to cancer through a process termed oncogene-induced senescence (OIS). They withdraw proliferating cells almost irreversibly, providing protection against malignant transformation. Now, a research team led by Daniel Peeper from the Netherland’s Cancer Institute in Amsterdam has identified a metabolic gate-keeper of the process.
Using metabolic and functional analyses of melanoma cells carrying the common BRAFV600E mutation, the team of Dutch, Scottish, Belgian, Spanish, Israeli and US researchers identified the TCA enzyme pyruvate dehydrogenase (PDH) as a crucial mediator of cancer senescence. BRAFV600E-induced senescence was accompanied by simultaneous suppression of the PDH-inhibitory enzyme pyruvate dehydrogenase kinase 1 (PDK1) and induction of the PDH-activating enzyme pyruvate dehydrogenase phosphatase 2 (PDP2). The resulting combined activation of PDH enhanced the use of pyruvate in the tricarboxylic acid cycle, causing increased respiration and redox stress.
Enforced normalisation of either PDK1 or PDP2 expression levels inhibited PDH and abrogated oncogene-induced senescence. Depletion of PDK1 eradicated melanoma subpopulations resistant to targeted BRAF inhibition, and caused regression of established melanomas. The results suggest a mechanistically new therapeutic route to induce cancer senescence and stop tumour cell proliferation at its earliest stages.
23.07.2014 In the largest genomic study published on any psychiatric disorder so far, researchers have indentified 83 new locations in the human genome associated with the risk of developing schizophrenia.
15.07.2014 British specialty pharma company Prostrakan is handing over £230m for Archimedes Pharma Limited, a company that brings its lead product Pecfent and its proprietary drug delivery technology platform into the deal.
11.07.2014 Among the seven newly launched Joint Technology Initiatives (JTI) of Horizon2020 are two with deep roots in biotech: IMI is going into its second round while the newly established Bio-based Industries partnership invests in bioeconomy.
04.07.2014 Genentech, a member of Swiss Roche Group, is set to acquire US-biotech Seragon Pharmaceuticals Inc. With the move, Genentech will obtain the rights to investigational breast cancer treatments.
03.07.2014 Nicox S.A. is stretching beyond the European market: The French eye health specialist is set to acquire Aciex Therapeutics Inc., a US-based pharma company with several ophthalmic therapeutics nearing market maturity.
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