Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computational analysis identifies drugs to treat drug-resistant breast cancer

01.08.2012
Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results, which are published in Molecular Systems Biology, reveal that the disruption of glucose metabolism is an effective therapeutic strategy for the treatment of tumours that have acquired resistance to front-line cancer drugs such as Lapatinib.

“The growth and survival of cancer cells can often be impaired by treatment with drugs that interfere with the actions of one or more oncogenes,” said Prahlad Ram, the senior author of the study and Professor at the University of Texas MD Anderson Cancer Center, Houston, Texas. “However, the clinical benefits to patients are often short lived due to acquired drug resistance. Finding alternative intervention points or so-called new addictions for cancer cells is of critical importance for designing novel therapeutic strategies against tumours. Our results reveal specific new targets for drug intervention in the metabolic pathways of cancer cells and identify existing drugs that can be used to treat drug-resistant cancer.”

Lapatinib is used for the treatment of patients with advanced or metastatic breast cancer in cases where tumours overexpress the ErbB2 gene. The ErbB2 gene provides instructions for making a specific growth factor receptor. If too much of this ErbB2 growth factor receptor is made, it can lead to cells that grow and divide continuously, one of the defining characteristics of breast cancer.

The scientists used microarrays to measure gene expression in breast cancer cells with and without treatment with Lapatinib. Computational analysis of more than 15000 gene interactions revealed four major populations of genes that were regulated in a significant way. Three of these groups were the regular suspects related to drug resistance, such as genes involved in oxidation and reduction reactions or cell cycle processes. A fourth group comprised a network of reactions linked to the deprivation of glucose.

Analysis of the gene expression networks of ErbB2-positive breast cancer patients revealed that the glucose deprivation network is linked to low survival rates of the patients. Computational screening of a library of existing drugs for therapeutics that target the glucose deprivation response identified several drugs that could be effective in treating drug-resistant breast cancer.

“By developing novel gene expression analysis algorithms and integrating diverse data, we have been able to look beyond changes in the immediate molecular signaling pathways of breast cancer cells and to consider the wider system of molecular networks within the cell,” remarked Ram. “Our approach predicts new uses for existing drugs that impact the metabolism of breast cancer cells and may offer an expedient route to improved treatments for breast cancer patients.”

The glucose-deprivation response network counteracts EGFR signalling in lapatinib resistant cells
Kakajan Komurov, Jen-Te Tseng, Melissa Muller, Elena G Seviour, Tyler J Moss, Lifeng Yang, Deepak Nagrath, Prahlad T Ram
Read the paper: doi: 10.1038/msb.2012.25
Further information on Molecular Systems Biology is available at
http://www.nature.com/msb
Media Contacts
Barry Whyte
Head | Public Relations and Communications
Tel: +49 6221 8891 108/111
communications@embo.org
About EMBO
EMBO stands for excellence in the life sciences. The organization enables the best science by supporting talented researchers, stimulating scientific exchange and advancing policies for a world-class European research environment.

EMBO is an organization of 1500 leading life scientist members that fosters new generations of researchers to produce world-class scientific results.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in cutting-edge techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.

Barry Whyte | EMBO
Further information:
http://www.embo.org
http://www.nature.com/msb

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

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...

Im Focus: Demonstration of a single molecule piezoelectric effect

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>