With your donations Wings for Ewing Sarcoma  is able to fund childhood cancer research projects for Ewing Sarcoma to further advance treatments protocols. Grants are reviewed, so you can trust that the money you give to this non-profit organization are used for beneficial and life-changing purposes. With your help we will be able to meet our mission goal and develop a plan that meets the demands for funding Ewing Sarcoma Research. 

 

2023 Research Grants:

Research Grant supporting the Vakoc Lab, the research focuses on high-throughput genetics to reveal vulnerabilities of the EWS-FLI1 oncoprotein.

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The Vacok lab recently discovered that ETV6 indirectly promotes tumor growth by modulating EWS-FLI1’s behavior in Ewing Sarcoma. In experiments in cancer cells and mice, the group showed that, in the absence of ETV6, EWS-FLI1 goes into overdrive. But rather than revving up tumor growth even further, EWS-FLI1’s extreme hyperactivity halts tumor growth. The hope is that these new insights can be used to develop a targeted drug that interferes with the interaction between ETV6 and EWS-FLI1 and might lead to an effective treatment for Ewing Sarcoma. The EWS-FLI1 oncoprotein is a compelling target for therapeutic intervention in Ewing Sarcoma, but drugs against this type of target are challenging to generate by the pharmaceutical industry.

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Dr. Vakoc's research is built on a premise in which a deep understanding of molecular function might allow for a new perspective on how ‘druggable’ the EWS-FLI1 target is, and he believes that technological advances made by the Vacok lab can achieve this goal. Specifically, their lab has invented new genetic tools for studying cancer-causing proteins like EWS-FLI1, and by applying these methods they believe it will be possible to ‘see’ what this protein is doing inside of cancer cells by revealing its atomic vulnerabilities. We are excited to be able to support this important work.

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From the Vakoc Lab: "Fundraising for pediatric cancer research can be challenging, owing to the relative rarity of these tumors when compared to the more common cancers that occur in adults. For this reason, our research into pediatric sarcoma is dependent on funds raised by foundations, often run by families or patients afflicted by these aggressive diseases. On behalf of the Vakoc lab at Cold Spring Harbor Laboratory, I would like to express my gratitude to the Wings for Ewing Sarcoma Foundation for supporting our research, which seek to advance novel targets for this tumor."

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2021 Research Grants:

Research Grant supporting Ewing Sarcoma zebrafish drug screen, using chemical libraries and a zebrafish model of Ewing Sarcoma, high throughput drug screens will be performed to identify potential new inhibitors. The goal of the research is to discover small molecule inhibitors that can be used in the treatment of Ewing Sarcoma with high efficacy in the prevention and treatment of metastasis with less toxicity than systemic chemotherapy.

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The recipient of this year's research grant is Dr. Alissa C. Baker, MD Assistant Professor of Pediatrics and Developmental and Molecular Biology at Albert Einstein College of Medicine / Montefiore Health Systems in New York.

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Dr. Baker’s research focuses on Ewing Sarcoma metastasis biology, with a specialized focus on Wnt signaling, using zebrafish as a model of sarcoma metastasis for high throughput drug screens to identify new agents, screening patient plasma and tissue samples for biomarkers of potential metastasis, and identifying circulating tumor cells in the blood of sarcoma patients as a possible correlative to disease burden.

 

Dr. Baker has identified a novel signaling pathway, Wnt signaling, most commonly recognized in early development, that allows Ewing sarcoma cells to migrate out from the primary tumor and into the bloodstream, specifically via the Wnt family member Wnt5a. Using human-derived Ewing sarcoma cell lines with genetic techniques to remove Wnt5a from the cells results in a complete change in their appearance, making them less adherent and less able to migrate. In addition, several proteins involved in cell motility are significantly decreased using a variety of techniques including fluorescent microscopy and assessments of individual proteins. These results demonstrate a direct interaction between Wnt5a and pro-motility signals within Ewing sarcoma cells that have never been reported, adding several new targets to potential therapeutic development.

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In addition, further studies using a zebrafish model of Ewing sarcoma also support this pathway model as Wnt5a-positive Ewing sarcoma cells can be visualized invading out of the primary tumors and into blood vessels. Treatment of zebrafish embryos which contain the Ewing sarcoma translocation with the pan-Wnt inhibitor demonstrate a decrease in blood vessel formation with several abnormal vessels formed. Preserved across numerous species is another important developmental pathway, Notch1 signaling, that controls blood vessel formation. Because the pan-Wnt inhibitor results in abnormal blood vessel formation in this Ewing sarcoma animal model, it is likely that the two pathways cooperate: Wnt5a signaling controls Ewing sarcoma cell migration, allowing the cells to break away from the primary tumor, while Notch1 signaling helps form primitive blood vessels to allow the Ewing sarcoma cells to enter the circulation and land in distant organs, the process of metastasis. Wnt signaling, Notch1 signaling, and proteins involved in this novel pathway are all potential new therapeutic targets.

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Using chemical libraries and a zebrafish model of Ewing sarcoma, Dr. Baker will perform high throughput drug screens to identify potential new inhibitors that can be translated into early phase I and II patient clinical trials. The ultimate goal of this research is to discover small molecule inhibitors that can be used in the treatment of Ewing sarcoma with high efficacy in the prevention and treatment of metastasis with less toxicity than systemic chemotherapy.

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A few words from Dr. Baker, “I am extremely grateful to the foundation Wings for Ewing Sarcoma for the generous funding towards this novel drug screen to identify new therapeutic targets in Ewing sarcoma. Unfortunately, despite research efforts, the overall survival for Ewing sarcoma, both localized and metastatic disease, has not changed in more than three decades. Federal funding only provides 4% of funds towards pediatric cancer research with the majority going towards adult cancer research. Therefore, physician-scientists such as myself, rely on the generous donations of foundations like Wings for Ewing Sarcoma to help propel our research forward to a better tomorrow for the lives of our patients and their families. Thank you for your support.”

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We are very excited to see how Dr. Baker’s research progresses from here on and will share some updates down the road. Thank you for your support. This would not have been possible without you!

 

 

2020 Research Grants:

Research Grant supporting the correlative biology in conjunction with *SARC037 Clinical Trial for Ewing Sarcoma patients.

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We are excited to announce another research grant we are supporting this year. The grant supports the correlative biology in conjunction with *SARC037 Clinical Trial for Ewing Sarcoma patients. (https://clinicaltrials.gov/ct2/show/NCT04067115)

 

Learning from clinical trials is of critical importance. Patrick Grohar, MD, PhD, a widely respected Ewing sarcoma researcher states that this effort of integrating extensive correlative biology in combination with a clinical trial for Ewing sarcoma relapse patients will be “a game changer”. The research, utilizing the expertise at four major research labs, will give insight into understanding the difference between patients who respond to therapy and those who do not. The leading-edge research includes detailed genotyping of the disease, analysis of circulating free tumor DNA, EWS-FLI1 transcriptome analysis, single cell RNA sequencing, circulating tumor cell RNA sequencing, and patient derived xenograft models. 

Wings for Ewing Sarcoma teamed up with three other foundations, 1 Million 4 Anna Foundation (TX) ,Teaming up to Fight Childhood Cancer (TX), and I-Rok Foundation (MO) to fund the full research (a total of $200,000) being conducted by the teams at Children’s Hospital of Philadelphia, Nationwide Children’s Hospital in Columbus, OH, Boston Children’s Hospital, and Children’s Hospital Colorado.

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More information on the study design from Dr. Grohar: “It has been known for more than 25 years that Ewing sarcoma cells are absolutely dependent on the EWS-FLI1 transcription factor for cell survival. Unfortunately, the clinical realization of an EWS-FLI1 targeted therapy has not been achieved. In this study, we will use trabectedin in combination with low dose irinotecan to therapeutically target EWS-FLI1. We have spent more than 10 years in the lab establishing exactly how this compound inhibits EWS-FLI1. We have used the information to determine the optimal dose and schedule of trabectedin/irinotecan administration that should realize the therapeutic suppression of EWS-FLI1 in patients. In addition, we have developed an imaging biomarker that should allow us to quantitate the suppression of EWS-FLI1 in patients in real time using a PET scan. Finally, we have designed the study to require pre- and post-treatment biopsies to confirm EWS-FLI1 suppression by more traditional assays. These biopsies will provide tissue that we will use to investigate the biology of relapsed disease using a variety of state-of-the-art assays and models.” Download and view the NOA letter here.

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Research Grant for Ewing Sarcoma Research to Dr. Brian Crompton at Dana-Farber Cancer Institute in Boston. 

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Dr. Brian Crompton is a physician-scientist at Dana-Farber Cancer Institute and his research focuses on finding new treatment approaches for patients with Ewing sarcoma who do not respond to the first line of treatment of VCD / IE chemotherapy or relapse patients. 

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In recent years, Dr. Crompton has found that Ewing sarcoma cancer cells are dependent on the activity of a protein called focal adhesion kinase also known as FAK. When FAK is inhibited, Ewing sarcoma cells die and cannot form tumors. Dr. Crompton is now partnering with a major pharmaceutical company that has multiple FAK inhibitors in clinical trials for adult tumors to complete necessary experiments to test the effects of FAK inhibition in a clinical trial for patients with Ewing sarcoma.

 

A few words from Dr. Crompton, “We are so excited to embark on a partnership with one of our heroes, Chiara Valle and her foundation, Wings for Ewing Sarcoma. We know that to break the trend of slow incremental progress in cancer care, we need to take on bold new research challenges. Together with Wings for Ewing Sarcoma, we will be able to test bold new ideas in the laboratory and then look to translate our findings into new treatment strategies for patients with Ewing Sarcoma.

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In the Crompton laboratory, we use high-throughput screening assays to identify novel combinations of targeted therapies, such as tyrosine kinase inhibitors, that work together to kill Ewing sarcoma cancer cells. Our screening approach treats cancer cells growing in culture dishes with drugs combined using a robotic liquid handling platform. Each candidate drug combination is tested against cell lines grown from Ewing sarcoma tumors donated by multiple patients. In this way, we hope to identify combinations that work for as many patients with Ewing sarcoma as possible. Once we identify potent treatment combinations, our goal is to work with our colleagues in the clinical research field to develop clinical trials to test the efficacy of these combinations for patients.

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The Crompton laboratory also specializes in utilizing novel DNA sequencing technologies to develop new non-invasive tests that can diagnose patients with Ewing sarcoma, predict their likelihood of treatment response, and identify relapses earlier than they can be detected with radiologic scans. These assays use a simple blood draw to detect the presence of minute amounts of tumor material floating in the blood of patients with cancer. Our first goal is to demonstrate that these “blood biopsies” are accurate and predictive. Once these tests are validated, our goal is to make these tests available in the clinic to improve decision making for to patients and their doctors.”

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We are very excited to see how Dr. Crompton’s research progresses from here on and will share some updates down the road. Thank you for your support. This would not have been possible without you!  View acknowledgement letter from Dana-Faber Cancer Institute.