Treatment resulted in tumor regression and a strong increase in survival without signs of toxicity.
The inhibitor, which recently entered trials in human cancer patients, thus seems to have therapeutic potential for BRCA-defective tumors. Sven Rottenberg, Piet Borst and Jos Jonkers publish their results this week in PNAS Online Early Edition.
Long-term treatment with AZD2281 in the mouse model did result in the development of drug resistance. This could however be reversed by coadministration of an other type of inhibitor, tariquidar. Furthermore, the researchers studied the effect of combined treatment with AZD2281 and cisplatin or carboplatin. This increased the recurrence-free and overall survival, suggesting that AZD2281 potentiates the effect of these DNA-damaging agents.
The researchers previously developed the mouse model to study BRCA1-associated breast tumors. BRCA1 defects are often observed in so called triple-negative tumors. No targeted therapy exists yet for this type of breast cancer, which account for about 15% of all breast tumors. The researchers now use the mouse model for preclinical evaluation of potential therapeutics that target tumors with BRCA1 defects and that might be useful for treatment of triple-negative cancers.
The results with AZD2281 show that the mouse model is not only useful for the investigation of the efficacy and toxicity of chemical compounds. Also the development, prevention and circumvention of drug resistance can be tested in the model.
Hence, intervention studies in the mouse model may help to predict the basis of resistance to novel therapeutics well in advance of the human experience. Ultimately, this may improve the clinical success rate for novel anticancer drugs.
Frederique Melman | alfa
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
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