Computational analysis identifies drugs to treat drug-resistant breast cancer

July 31, 2012
The image shows a computationally generated map of some of the cellular processes involved in glucose metabolism for breast cancer cells. Credit: Prahlad Ram, University of Texas MD Anderson Cancer Center. Adapted by Uta Mackensen, EMBO.

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 . 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 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 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 .

The scientists used microarrays to measure gene expression in 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."

Explore further: Researchers identify mechanism that makes breast cancer invasive

More information: The glucose-deprivation response network counteracts EGFR signalling in lapatinib resistant cells, doi: 10.1038/msb.2012.25

Related Stories

Researchers identify mechanism that makes breast cancer invasive

March 29, 2012
A new study has identified a key mechanism that causes breast cancer to spread. The research, published by Cell Press on March 30th in the journal Molecular Cell, enhances our knowledge about the signals that drive cancer ...

Novel approach to treating breast cancer shows great promise

December 7, 2011
In a novel therapeutic approach to treating breast cancer, Loyola University Medical Center researchers are reporting positive results from a clinical trial of a drug that targets tumor stem cells.

Gene therapy kills breast cancer stem cells, boosts chemotherapy

September 12, 2011
Gene therapy delivered directly to a particularly stubborn type of breast cancer cell causes the cells to self-destruct, lowers chance of recurrence and helps increase the effectiveness of some types of chemotherapy, researchers ...

Another step toward resisting breast cancer

September 21, 2011
Medical researchers at the University of Leeds have come a step closer to understanding how to stop breast cancers from coming back.

Scientists find new drug target in breast cancer

May 22, 2011
Researchers have identified a new protein involved in the development of drug resistance in breast cancer which could be a target for new treatments, they report today in the journal Nature Medicine.

Recommended for you

Sensor-equipped pill raises technological, ethical questions

November 17, 2017
The first drug with a sensor embedded in a pill that alerts doctors when patients have taken their medications was approved by the Food and Drug Administration, raiding issues involving privacy, cost, and whether patients ...

New painkillers reduce overdose risk

November 16, 2017
Scientists on the Florida campus of The Scripps Research Institute (TSRI) have developed new opioid pain relievers that reduce pain on par with morphine but do not slow or stop breathing—the cause of opiate overdose.

Separating side effects could hold key for safer opioids

November 16, 2017
Opioid pain relievers can be extremely effective in relieving pain, but can carry a high risk of addiction and ultimately overdose when breathing is suppressed and stops. Scientists have discovered a way to separate these ...

US regulators approve first digital pill to track patients

November 14, 2017
U.S. regulators have approved the first drug with a sensor that alerts doctors when the medication has been taken, offering a new way of monitoring patients but also raising privacy concerns.

Introduction is different, but top medications for opioid addiction equally effective

November 14, 2017
With opioid addiction officially declared a public health emergency in the U.S., medical intervention to treat the illness is increasingly important in responding to the epidemic. Now, a new study concludes that two of the ...

Drugstore pain pills as effective as opioids in ER patients

November 7, 2017
Emergency rooms are where many patients are first introduced to powerful opioid painkillers, but what if doctors offered over-the-counter pills instead? A new study tested that approach on patients with broken bones and sprains ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.