Aussie university halts trials of skin cancer drug whose developer has four retractions
An Australian university has put a hold on trials of an experimental drug for skin cancer whose main developer has been dogged by charges of research misconduct for several years.
The Australian Broadcasting Corporation is reporting that the University of New South Wales has suspended trials of the drug, DZ13, while it investigates the work of Levon Khachigian, who is leading the studies.
According to the news organization, Khachigian and his group were cleared by the school in two prior inquiries. However, additional accusations of misconduct — specifically involving image manipulation and misuse — prompted a third investigation.
We’ve found four retractions of Khachigian’s studies, from the Journal of Biological Chemistry and Biochemical and Biophysical Research Communications, between 2009 and 2010 (before the launch of Retraction Watch).
1. Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1beta and forms a cytokine-inducible gene-silencing complex with NF-kappab p65 and interferon regulatory factor-1. (cited five times, according to Thomson Scientific’s Web of Knowledge)
Liu MY, Khachigian LM.
J Biol Chem. 2009 Dec 11;284(50):35101-12. doi: 10.1074/jbc.M109.061903. Epub 2009 Oct 20. Erratum in: J Biol Chem. 2010 Feb 5;285(6):4263. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
2. Injury-induced platelet-derived growth factor receptor-alpha expression mediated by interleukin-1beta (IL-1beta) release and cooperative transactivation by NF-kappaB and ATF-4: IL-1beta facilitates HDAC-1/2 dissociation from promoter. (cited six times)
Zhang N, Khachigian LM.
J Biol Chem. 2009 Oct 9;284(41):27933-43. doi: 10.1074/jbc.M109.025742. Epub 2009 Jul 31. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
Zhang C, Song QH, Khachigian LM, Lubenec I, Shie JL, Yang B, Li J, Tian Y.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):689-94. doi: 10.1016/j.bbrc.2009.01.151. Epub 2009 Jan 29. Retraction in: Biochem Biophys Res Commun. 2009 Oct 16;388(2):464.
Kavurma MM, Bobryshev Y, Khachigian LM.
J Biol Chem. 2002 Sep 27;277(39):36244-52. Epub 2002 Apr 22. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
This article has been withdrawn by the authors.
But there was this earlier errata for “Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1β and forms a cytokine-inducible gene-silencing complex with NF-κB p65 and interferon regulatory factor-1″:
The published version of the left panel of Fig. 4C inadvertently duplicated the first five lanes from the right panel of Fig. 2A. The correct version of Fig. 4C is shown below.
In the published version of Fig. 6B, the fourth panel was inadvertently duplicated as the sixth panel. The correct version of Fig. 6B is shown below.
These additions and corrections do not result in any change in the conclusions of the article.
Researchers — including David Vaux — have raised questions about another 2010 article in the JBC. That paper’s not identified, but we think it might be “c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins,” which appeared that year.
The ABC quotes Kachigian saying:
the research was not flawed. The independent inquiry panel found no case of research misconduct, nor any evidence of falsification, fabrication or misrepresentation of data.
The story gets pretty gnarly, so it’s worth reading ABC’s coverage.