A research team from the University of Cologne has identified a new approach for treating particularly aggressive pancreatic cancer. It makes use of a genetic mutation that allows the immune system to attack the cancer cells again / publication in ‘Nature Communications’ Quelle: IDW Informationsdienst Wissenschaft

Ein Kölner Forschungsteam identifiziert einen neuen Therapieansatz gegen den besonders aggressiven Bauchspeicheldrüsenkrebs. Der Ansatz nutzt eine genetische Mutation aus, um dessen Zellen für das Immunsystem wieder angreifbar zu machen / Veröffentlichung in „Nature Communications“ Quelle: IDW Informationsdienst Wissenschaft

Intrahepatische Cholangiokarzinome (iCCAs) gehören zu den bösartigsten Krebserkrankungen weltweit. Trotz Fortschritten in der Systemtherapie bleiben Optionen begrenzt, weshalb neue Strategien dringend benötigt werden. Eine Studie um Prof. Dr. Jens Marquardt vom UKSH Lübeck zeigt nun, dass die Aktivierung von PARP-1 eine zentrale Rolle in KRAS-mutierten iCCAs spielt – einer Mutation, die mit einer besonders schlechten Prognose verbunden ist. Durch die gezielte Hemmung von PARP-1 konnte das Tumorwachstum in präklinischen Modellen deutlich reduziert werden. Diese Ergebnisse eröffnen neue Ansätze für personalisierte Therapien. Die Wilhelm Sander-Stiftung unterstützte das Projekt mit 180.000 €. Quelle: IDW Informationsdienst Wissenschaft

Muhammad A Shah, Emily L Denton, Cheryl H Arrowsmith, Mathieu Lupien and Matthieu Schapira Abstract Background The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients. Results Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover…

Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming Wallace hypothesized mitochondrial dysfunction as a central role in a wide range of age-related disorders and various forms of cancer. Steadily rising increases in mitochondrial DNA mutations cause abrupt shifts in diseases. Discrete changes in nuclear gene expression in response to small increases in DNA mutant level are analogous to the phase shifts that is well known in physics: As heat is added, the ice abruptly turns to water or with more heat abruptly to steam. Therefore, a quantitative change that is an increasing proportion of mitochondrial DNA mutation results…

Tomasetti and Vogelstein show that the lifetime risk of cancers of many different types is strongly correlated with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to bad luck, that is, random mutations arising during DNA replication in normal, noncancerous stem cells. Tomasetti C, Vogelstein B (2015): Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2 January 2015:…