How Cancer Cells May Develop Resistance to FGFR Inhibitors

A new study by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) has identified a mechanism by which cancer cells develop resistance to a class of drugs called fibroblast growth factor receptor (FGFR) inhibitors.

The study, published in the journal Molecular Cancer Therapeutics, also found that use of a second inhibitor might improve the effectiveness of these drugs by possibly preventing resistance, and it recommends that clinical trials should be designed to include a second inhibitor.

FGFR inhibitors are a new family of targeted agents designed to inhibit the action of the fibroblast growth factor receptor, which is often overexpressed in lung, bladder, biliary and breast cancers.

“Understanding how drug resistance develops can help in the design of new agents or strategies to overcome resistance,” says principal investigator Sameek Roychowdhury, MD, PhD, assistant professor of medicine and of pharmacology in the Division of Medical Oncology at the OSUCCC – James.

“Our paper demonstrates in a laboratory model how cancer can evade this class of therapy, and it provides insights into how clinical trials for these therapies could be further developed to overcome the problem of drug resistance,” he adds.

The laboratory study by Roychowdhury and his colleagues induced resistance to the FGFR inhibitor BGJ398 in lung- and bladder-cancer cells after long-term exposure to the agent. The researchers then found that, while the drug continued to inhibit FGFR activity in the resistant cells, its inhibition of FGFR signaling had no appreciable effect on the cells’ survival.

Examining other molecules in the FGFR pathway, the researchers found that a regulatory protein called Akt remained highly active, even during FGFR inhibition. Akt, a key regulator of cell biology, is directly involved in cell proliferation, cell survival and cell growth.

Furthermore, they found that by inhibiting Akt they could significantly slow cell proliferation, cell migration and cell invasion in the lung cancer and bladder cancer cells.

“Fibroblast growth factor receptor inhibitors are new therapies being developed in clinical trials for patients whose cancer cells have genetic alterations in this family of genes,” says Roychowdhury, a member of the OSUCCC – James Translational Therapeutics Program. “We believe our findings will help improve this therapy for lung, bladder and other cancers.”

Source: OSUCCC – James

Treatment of malignant brain tumor in children gets closer

malignant brain tumour
Picture: University of Copenhage

Researchers at the University of Copenhagen have identified important mechanisms underlying how a special type of malignant brain tumor arises in children. Not only do these discoveries give researchers important information about the tumor but they could also result in possible treatment.

DIPG (Diffuse Intrinsic Pontine Glioma) is a rare malignant cerebral tumor in children. It has only a 1% 5-year survival rate, amongst other things because it is not possible to operate because the tumor is located in the brain stem. Danish researchers have now just published a study in an international journal, Nature Medicine, in which they have investigated the molecular mechanisms that could be the reason why the malignant tumor arises and develops.

”DIPG is a terrible disease with very poor survival. Before we can identify a treatment, we need to understand the mechanisms underlying the formation and growth of the tumor. We have now made a major step forward and we also have ideas for possible treatment,” says Prof. Kristian Helin, Director of the Biotech Research and Innovation Center.

DIPG tumors are a type of cancer in which there are mutations in the so-called histone proteins. One of these is the H3K27M protein that could be the cause of the malignant brain tumor. In order to identify the specific mechanisms, researchers created a special mouse model based on the same genetic changes found in the brain tumor. This enabled them to gain a general understanding of the behaviour of the tumor and also to test possible treatments.

Source: University of Copenhagen

By Brückenkopf GmbH – Free online medical devices trade fair

Rapid Detection of Zika Virus at Airports and Other Sites

Zika Virus Detection

About the size of a tablet, a portable device that could be used in a host of environments like a busy airport or even a remote location in South America, may hold the key to detecting the dreaded Zika virus accurately, rapidly and inexpensively using just a saliva sample. While scientists across the world are scrambling to find some sort of immunization, researchers from Florida Atlantic University are working to develop a diagnostic tool to reduce the impact of the outbreak until a vaccine is identified.

“Most of the Zika cases in the United States and especially in Florida are travel related,” said Waseem Asghar, Ph.D., lead investigator and assistant professor at the Department of Computer and Electrical Engineering and Computer Science in FAU’s College of Engineering and Computer Science and in the Department of Biological Sciences in FAU’s Charles E. Schmidt College of Science. “We are working to develop a tool that can be used without expensive laboratory equipment and skilled technicians in various settings like an airport or a community health center to provide reassurance to expectant families and those concerned because of recent travel. For about $2 and within 15 minutes, we hope to accurately determine whether or not an individual has an active infection.”

Currently, patients are diagnosed by testing whether they have antibodies against the Zika virus in their bloodstream, however, the antibody test cannot discriminate accurately between the Zika virus and other flaviviruses such as Dengue, West Nile virus and Chikungunya. The more accurate method for detecting the virus is by looking for pieces of the viral genome in a patient’s blood sample using a test known as polymerase chain reaction (PCR). PCR is costly ($20,000+), bulky and requires highly skilled laboratory personnel to operate. Furthermore, results for PCR testing can take hours to yield results.

More information: Brückenkopf GmbH

HIV test performed on USB stick

The device, created by scientists at Imperial College London and DNA Electronics, uses a drop of blood to detect HIV, and then creates an electrical signal that can be read by a computer, laptop or handheld device.

The disposable test could be used for HIV patients to monitor their own treatment.

Furthermore, the technology could enable patients with HIV to be managed more effectively in remote locations.

Continue reading “HIV test performed on USB stick”

Zika Virus Responds to Three Existing Drugs in Lab Study

Scientists report that a specialized drug screen test using lab-grown human cells has revealed two classes of compounds already in the pharmaceutical arsenal that may work against mosquito-borne Zika virus infections.

In a summary of their work, published in Nature Medicine on Aug. 29, the investigators say they screened 6,000 existing compounds currently in late-stage clinical trials or already approved for human use for other conditions, and identified several compounds that showed the ability to hinder or halt the progress of the Zika virus in lab-grown human neural cells.

Continue reading “Zika Virus Responds to Three Existing Drugs in Lab Study”

Diabetes: new hope for better wound healing

Diabetics often have to contend with wounds that heal poorly. Researchers at the Max Planck Institute for Biology of Ageing, the CMMC, the CECAD Excellence Cluster and the Institute of Genetics of the University of Cologne have now gained new insights into the underlying cellular mechanisms. Their findings could lead to the development of new treatment methods.

Time-lapse of a wound healing in Drosophila (from left to right): After removal of the nucleus (in yellow) the cell membrane (in pink) seals off the gap caused by the wound. You can order this photo from us by phone or e-mail. contact details appear below.
Time-lapse of a wound healing in Drosophila (from left to right): After removal of the nucleus (in yellow) the cell membrane (in pink) seals off the gap caused by the wound. You can order this photo from us by phone or e-mail. contact details appear below.

According to estimates by the International Diabetes Federation (IDF), some six million people in Germany suffer from diabetes mellitus, around 90 percent of whom have the type 2 form. The disease, which is triggered by a disturbance of insulin metabolism, has serious effects on the entire body. One problem these patients face is poor wound healing.

It had previously been assumed that high levels of glucose in the blood damages vessels and neurons and impairs the immune system, thereby accounting for the wound-healing problems. A Cologne-based research group headed by Linda Partridge, Director of the Max Planck Institute for Biology of Ageing, and Maria Leptin, professor at the Institute of Genetics of the University of Cologne, has now presented in a study that slowed insulin metabolism at the wound site directly affects neighbouring cells involved in wound healing.

Investigations of fly skin Parisa Kakanj, the author of the study, examined the skin of larvae of the fruit fly Drosophila melanogaster. These flies serve as models for diabetes, because insulin metabolism has been strongly conserved over the course of evolution, meaning that flies and mammals are very similar in this respect. Using a precision laser, Kakanj removed a cell from the outermost skin layer of fruit fly larvae and then observed what happens in the neighbouring cells live under the microscope.

“Immediately after a skin injury, the neighbouring cells respond by forming an actomyosin cable,” Kakanj explains. The cable consists of proteins that otherwise occur in muscle fibres, where they are responsible for muscular contraction. After an injury, the cable forms a contractile ring around the wound. It then contracts, sealing off the gap caused by the wound. “However, if insulin metabolism is impaired, as in our genetically modified flies, the cable is weaker and forms much later. This results in incomplete or slow wound healing,” as Kakanj relates.

New treatments for impaired wound healing could precisely target this mechanism. “Our findings raise hope of a potential treatment for diabetics. In future, it may be possible to treat wound sites with drugs that locally activate insulin metabolism,” Kakanj explains. The research team is now working closely with Sabine Eming, a senior dermatologist at the clinic and polyclinic for dermatology and venereology at the University Hospital Cologne, the CMMC and the Excellence Cluster for Ageing Research at the University of Cologne in order to investigate ways to implement this approach.

Source: University of Cologne / Universität zu Köln