Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results 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 over-express 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 EMBO

Scientists have identified a group of small molecules that interfere with the activity of a compound that initiates multiple steps in blood clotting, including those that lead to the obstruction of veins or arteries, a condition called thrombosis. Blocking the activity of this compound, polyphosphate, could treat thrombosis with fewer bleeding side effects than the drugs that are currently on the market.
Blood clots are formed at the site of an injured blood vessel to prevent blood loss. Sometimes, however, blood clots completely clog an artery or vein and the surrounding tissues are damaged. The U.S. Centers for Disease Control and Prevention reports that annually, 300,000 to 600,000 Americans are afflicted with deep vein thrombosis or pulmonary embolism, a blocked lung artery that often results from thrombosis, and 60,000 to 100,000 people die each year as a result of these conditions.
There are two pathways that trigger blood clotting. The tissue factor pathway helps stop bleeding if a person is injured. If any of the proteins of this pathway are missing, a bleeding problem will develop. In contrast, the contact pathway is activated when blood comes into contact with some artificial substances. Although this pathway can cause pathological blood clots, humans who lack proteins in this pathway do not have bleeding problems. These two pathways eventually converge to form a common pathway.
In 2006, the researchers found that compounds called polyphosphates can, when released from cell fragments called platelets, activate the contact pathway, said University of Illinois biochemistry professor James H. Morrissey, who led that study and the new analysis.
Because the contact pathway is not essential for normal blood clotting after an injury, interrupting polyphosphate ‘wouldn

A new study by University of North Carolina School of Medicine researchers found that 31 percent of children identified as at risk for autism spectrum disorders (ASD) at 12 months received a confirmed diagnosis of ASD by age 3 years.
In addition, 85 percent of the children found to be at risk for ASD based on results from the First Year Inventory (FYI), a 63-item questionnaire filled out by their parents, had some other developmental disability or concern by age three, said Grace Baranek, PhD, senior author of the study and an autism researcher with the Program for Early Autism, Research, Leadership and Service (PEARLS) in the Department of Allied Health Sciences at the UNC School of Medicine.
‘These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention,’ she said.
Lead author of the study, Lauren Turner-Brown, PhD, also a researcher with PEARLS and the Carolina Institute for Developmental Disabilities said, ‘Identification of children at risk for ASD at 12 months could provide a substantial number of children and their families with access to intervention services months or years before they would otherwise receive a traditional diagnosis.’
The First Year Inventory was developed by Grace Baranek, PhD, Linda Watson, EdD, Elizabeth Crais, PhD and J. Steven Reznick, PhD, who are all researchers with PEARLS. All are also co-authors of the study with Turner-Brown, published online ahead of print.
In the study, parents of 699 children who had completed the FYI when their child was 12 months old completed additional screening questionnaires when their child reached age 3. In addition, children who were found to be at risk for ASD based on these measures were invited for in-person diagnostic evaluations.
‘These findings are encouraging and suggest promise in the approach of using parent report of infant behaviours as a tool for identifying 12-month-olds who are at risk for an eventual diagnosis of ASD,’ Turner-Brown said. University of North Carolina Health Care

A pioneering surgical blood salvage technology developed at the University of Strathclyde, Glasgow, is set to transform the way major surgery is carried out by reducing blood loss in patients.

HemoSep is set to revolutionise the health care sector after gaining the CE mark and receiving Canadian national approval, following highly successful clinical trials in the world leading University of Kirikkale University Hospital in Ankara, Turkey.

The device is designed to recover blood spilled during open-heart and major trauma surgery and concentrate the blood cells for transfusion back to the patient. This process, known as autotransfusion, reduces the volume of donor blood required and the problems associated with transfusion reaction.

Professor Terry Gourlay, who led the development of the technology at the University