Computational analysis identifies drugs to treat drug-resistant breast cancer

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."

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

add to favorites email to friend print save as pdf

Related Stories

Herceptin targets breast cancer stem cells

Jul 09, 2008

A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor's growth and spread, according to a new study from the University of Michigan Comprehensive ...

Recommended for you

FDA warning: men's testosterone drugs overused (Update)

Mar 03, 2015

The Food and Drug Administration is warning doctors against over-prescribing testosterone-boosting drugs for men, saying the popular treatments have not been established as safe or effective for common age-related ...

Early benefit assessment increases transparency for study data

Mar 03, 2015

Four years have passed since the introduction of the German Act on the Reform of the Market for Medicinal Products (AMNOG). AMNOG was primarily aimed at containing the increasing drug expenditure of the statutory health insurance ...

User 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.