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
First line of defence against influenza further decoded
21.02.2018 | Helmholtz-Zentrum für Infektionsforschung
Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates
21.02.2018 | Institute of Science and Technology Austria
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Physics and Astronomy
21.02.2018 | Physics and Astronomy
21.02.2018 | Earth Sciences