|Project||Purpose||Annual Costs (US$)||Total Costs|
|Year 1||Year 2||Year 3||Year 4||Year 5|
|1||Additional Researcher||Increase Dr Rubin’s EHE Team and so accelerate the program.||Funded||100,000||100,000||100,000||100,000||100,000|
|2||Genetic Screening||To identify which EHE tumors will be aggressive.||60,000||60,000||60,000||60,000||60,000||300,000|
|3||Cell line /mouse model||Develop biological models to allow testing of EHE theories.||50,000||50,000||50,000||50,000||50,000||250,000|
|4||Drug Screening||Screen a large number of drugs to identify those that will have a positive impact.||Total cost estimated at US $150,000, but this is currently the subject of an independent
grant application is not included here.
|5||Blood and tissue banking||Collect EHE tissue and blood samples to support current and future research.||90,000||test||test||test||test||90,000|
|6||Biomarkers||Identify compounds in blood to signal change in state of EHE in patients.||Funded||60,000||60,000||60,000||60,000||300,000|
|7||Immunotherapy||Evaluate immunotherapy treatments to identify successful regimens.||Funded||50,000||100,000||100,000||100,000||450,000|
|8||Hormone Involvement||Evaluate type and mechanism of hormone involvement in EHE||30,000||30,000||30,000||test||test||90,000|
|Total Annual Funding Requirement||340,000||400,000||400,000||370,000||370,000||1,880,000|
Funding of additional researcher to Dr. Rubin’s Lab
The EHE Group were delighted to be able to provide the required sum of $180K to Dr Rubin in February 2016 which resulted in hiring of an additional researcher.
Dr Rubin is studying the genetics of EHE to understand which tumors will be aggressive and which will be indolent. This is a fundamental question that is key to the management of EHE. Molecular analysis will focus on genetic mutations that collaborate with the gene fusion. The hypothesis of this work is that different genetic mutations collaborate with WWTR1-CAMTA1 to alter the clinical course. The goal of this analysis is to identify the genes that predict which lesions will become aggressive (so-called prognostic biomarkers).
Cell line/mouse model
To study cancer, it is necessary to develop biological models. Currently, however, no such biological models are available. Dr Rubin is pursuing a ‘two-pronged’ strategy to remedy this situation. The first approach is to grow human EHE specimens in plastic dishes. Once these cultures are established, they can be frozen and thawed whenever it is necessary to study live EHE cells.
The second approach will to develop an EHE animal model using the humble mouse. To make this model, the research team has designed and is in the process of making a genetically engineered EHE mouse. Once a mouse EHE model is developed, an unending source of mouse EHE samples will be available to study, overcoming the rarity of human EHE tissue.
Therapeutic drug screening
Response of EHE patients to different regiments is inconsistent.Dr Rubin will use an EHE cell model developed within his laboratory to screen libraries of therapeutic compounds.The key to the success of drug screening is putting a lot of thought and planning into the front end of the process by developing an assay with high throughput, excellent selectivity, and high specificity.Once the assay has been tested it is relatively straightforward to scale up and test hundreds of thousands of compounds. As a result of this assay being unbiased, the only result sought from the compounds tested is that they inhibit, or activate a biological process that the researchers believe will impact EHE growth. This assay has the potential to discover novel therapies!
Tissue and Blood Banking
The rarity of EHE means that one of the fundamental difficulties for researchers is accessing tissue and blood samples for use within their projects. It has therefore been agreed that initiating tissue and blood banking at recognised locations will allow such samples to be collated and stored over time so that samples may be more readily available when required.
Liquid biopsy and liquid biomarkers
One of the biggest challenges facing doctors treating EHE patients is to identify the correct time to initiate therapy.Unpredictable EHE behavior can sometimes result in the doctors missing the critical window when EHE might be more likely to respond to therapy.There is however a strong likelihood that EHE progression can be more readily identified from patients’ blood samples taken in between periodic scans. Such an approach has already been proven for other cancers. The state of a patient’s cancer is monitored by monitoring for increasing levels of circulating free DNA in the blood, or increasing levels of certain proteins that are proven to either stimulate cancer growth or result from cancer progression
One characteristic seen in a small number of EHE patients is the spontaneous regression of EHE tumors in some cases until they have completely disappeared. The oncological community agrees that the most rational explanation for this phenomena is the activation of the patient’s own immune system and the resultant successful recognition and elimination of cancer cells.
In addition,we already have several cases EHE patients have shown a good response to immunotherapy.
We are absolutely thrilled that one of the most distinguished researchers in immuno oncology Dr. Robert Schreiber agreed to be a principal investigator in the project that will cover a broad spectrum of immuno evaluation of EHE . The project will include a genetic profiling of many EHE samples in order to create a genetic immunoprofile of EHE , identification of best immunotherapy regimens and development of personalized immuno vaccine for EHE patients.
This project will evaluate the apparent greater tendency of EHE to present in young adult women, with a clinical signal that there may be a link with pregnancy. While the clinical signal suggests there is probably a connection with hormones and the onset of EHE, there is currently no knowledge of what this connection may be. Hormonal influence on cancer is a known phenomenon.