ThyCa News

ThyCa Awards 5 New Research Grants

11/2019

ThyCa is excited to announce five new thyroid cancer research grants, for projects that center on differentiated thyroid cancer (papillary, follicular), medullary thyroid cancer, and anaplastic thyroid cancer. ThyCa also awarded continuation grants to additional research projects.
 
ThyCa awarded four of these new grants in cooperation with the American Thyroid Association (ATA), including one grant co-funded with Bite Me Cancer. An independent research committee of the ATA selected the grant recipients based on the best research proposals submitted.
 
ThyCa awarded the fifth new grant in cooperation with the American Association of Endocrine Surgeons; its research committee selected the recipient.
 
The new grant recipients are researchers at these centers:
  • Brigham and Women's Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts
  • Medstar Georgetown University Hospital, Washington, District of Columbia
  • National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • University of Texas MD Anderson Cancer Center, Houston, Texas
  •  Vanderbilt University Medical Center, Nashville, Tennessee 
"Generous donations, both small and large, from ThyCa supporters made these grants possible," said ThyCa Executive Director Gary Bloom, himself a thyroid cancer survivor. "We are extremely grateful to all our donors for your generosity and commitment to advancing our mission of finding cures for all thyroid cancer."
 
Introducing the 2019 Grant Awardees and their Projects

Project Title: Defining the Role of SWI/SNF Mutations in Anaplastic Thyroid Carcinoma

Grant Recipient: Jennifer Wang, M.D., Sc.M., Assistant Professor, University of Texas MD Anderson Cancer Center, Houston, Texas.

Recent findings suggest that mutations in epigenetic pathways play a role in the development of anaplastic thyroid cancer (ATC). While SWI/SNF mutations are rare events in papillary thyroid cancer (PTC), they have been reported in 18-36% of ATCs, suggesting that SWI/SNF mutations occur during the transformation of PTC to ATC. While ATC can arise on its own, evidence suggests that the majority of ATCs develop from differentiated thyroid carcinoma as a result of de-differentiating event. Prior studies have been limited by small ATC sample sizes and incomplete coverage of SWI/SNF genes by targeted panels. This project will use a much larger sample size and determine the frequency of SWI/SNF subunit mutations and relationships with other driver genes. It will also determine whether SWI/SNF alterations drive the dedifferentiation of PTC to ATC and evaluate potential therapeutic targets based on synthetic lethal interactions involving SWI/SNF subunits in SWI/SNF-mutated ATC.

About Dr. Wang. Dr. Wang earned her M.D. from University of Toronto, Ontario, Canada, and her SC.M. from Johns Hopkins University, Baltimore, Maryland. She further training at the University of Toronto and University of Texas MD Anderson Cancer Center. She is an Assistant Professor in the Department of Head and Neck Surgery at MD Anderson Cancer Center. Her clinical and research interests focus on aggressive thyroid cancers.
 
Project Title: Immunologic Markers of Aggressive Thyroid Carcinoma

Grant Recipient: Vivian Weiss, M.D., Ph.D., Assistant Professor, Vanderbilt University Medical Center, Nashville, Tennessee.

With increasing thyroid cancer detection, there is concern that indolent thyroid tumors are being over-treated. However, it's not possible to predict which differentiated tumors can be monitored with active surveillance and which require more aggressive treatment. Some well-differentiated thyroid cancers develop into metastatic and de-differentiated disease. There are still relatively few molecular markers predictive of aggressive thyroid tumor behavior. For many cancer types, the tumor immune microenvironment plays an important role in tumor behavior. However, for thyroid cancer, the immune microenvironment and its role in cancer progression are poorly understood. Improved understanding of the microenvironment may lead to novel biomarkers and therapeutics for advanced thyroid cancer. This project hypothesizes that certain immune cell infiltrates in thyroid cancer contribute to the development of aggressive disease. Preliminary studies indicate that more aggressive tumors have increased tumor-infiltrating neutrophils, macrophages, and dendritic cells. This study will complete next-generation sequencing of 350 thyroid resection specimens, develop an immune model for predicting aggressive disease, and discover the role of tumor-infiltrating immune cells in the growth and metastasis of thyroid carcinoma.

About Dr. Weiss. Vivian Weiss, M.D., Ph.D., earned her M.D. and Ph.D. at Johns Hopkins University in Baltimore, Maryland, followed by residency training at Vanderbilt University Medical Center, where she is now an Assistant Professor in the Department of Pathology, Microbiology, and Immunology. In 2017 she received the American Society of Cytopathology Young Investigator Award. Her research focuses on molecular alterations and tumor microenvironment of thyroid cancer, to improve current diagnostic and treatment approaches.

Project Title: Targeting Mitochondrial Cytochrome-C-Oxidase for The Treatment of Medullary Thyroid Cancer (MTC).

Grant Recipient: Athanasios Bikas, M.D., Chief Medical Resident, Medstar Georgetown University Hospital, Washington, District of Columbia.
 
Metabolic reprogramming of tumor cells is being increasingly recognized as an important disease driver. The pharmacological targeting of mitochondrial functions has emerged as a promising tool for treatment of cancer. This project will explore the role of mitochondria in MTC. This team's earlier experiments indicated that targeting of mitochondrial complex IV could be an effective strategy for the treatment of MTC, which accounts for 3 - 5% of thyroid cancers, but 14% of thyroid cancer deaths The nuclear-encoded subunit 4 of cytochrome-c-oxidase (COX4) appears to play a critical role in regulation of oxidative phosphorylation and contributes to proliferation of MTC cells. Targeting COX4 with Chlorpromazine may represent a novel strategy for the treatment of patients with MTCs. This project aims to (1) Determine the role of RET signaling in the regulation of genes controlling mitochondrial respiration in MTC cells; 2) Determine the role of COX4 for development of MTC in vivo, and examine the effects of COX4 inhibition on MTC cell growth in an animal model; and 3) Correlate expression of genes controlling mitochondrial respiration with oncogene mutations in human medullary thyroid cancers.

About Dr. Bikas. Dr. Bikas graduated from University of Athens, Greece, Faculty of Medicine. He undertook further studies in Molecular Biology from the University of Athens, and in thyroid cancer clinical and basic research, under supervision of Kenneth Burman, M.D., Leonard Wartofsky , M.D., and Vasyl Vasko, M.D. He has several first author publications in medical journals and has received regional and national awards. After his medical residency at MedStar Georgetown University Hospital , he was named a Chief Medical Resident.
 
This grant to Dr. Bikas is co-funded by ThyCa, and Bite Me Cancer in cooperation with the American Thyroid Association.

Project Title: Glutamine Metabolism Is a New Therapeutic Target in Thyroid Cancer
This grant is the Ric Blake Memorial Thyroid Cancer Research Grant, named in honor of one of ThyCa's Co-Founders. This ThyCa grant is awarded in cooperation with ATA.

Grant Recipient: Myriem Boufraqech, M.D., Ph.D., Surgical Oncology Group, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
 
The most common and frequent mutation in thyroid cancer is BRAFV600E. It is present in approximately 40% of primary papillary thyroid cancer, 80% of recurrent papillary thyroid cancer, and 25% of anaplastic thyroid cancer (ATC). A total of 10-15% of patients with differentiated tumor will develop recurrences with more aggressive phenotypes and distant metastases. They have a poor prognosis, with 10-year overall survival rate of 10%. Median survival for ATC is from 3 to 6 months. Despite the increased use of kinase inhibitors to treat disease progression, the drug resistance and side effects have led to a lack of response in these aggressive tumors. Overcoming acquired resistance to BRAFV600E inhibitors is critical for improving patient outcomes.
 
Metabolic reprogramming in cancer cells has been shown to be a key regulator of the mechanisms of drug resistance. Thus, a good strategic approach to overcome drug resistance in BRAF mutated thyroid cancers includes metabolic modulation via glutaminolysis to induce the anti-tumor response to BRAFV600E inhibitor and the targeting of glutamine metabolism in aggressive thyroid cancer overexpressing mitochondrial glutaminase.
 
This research will study in vivo anti-tumor efficacy of the glutaminase inhibitor (CB-839) and evaluate the role of glutamine metabolism in thyroid cancer progression, metastasis, and drug resistance.
 
About Dr. Boufraqech. Dr. Boufraqech earned her Ph.D. in Molecular and Cellular Biology in the Laboratory of Thyroid Carcinogenesis of Cancer Center Gustave Roussy at University of Paris-Sud XI in Paris, France. She received further training at the National Cancer Institute (NCI), National Institutes of Health, in Bethesda, Maryland. She has authored more than 30 research papers. She was appointed as a junior NCI faculty member. Her research focuses on molecular pathophysiology of aggressive thyroid cancer and the identification of novel effective targeted therapy in metastatic thyroid cancer.
Project Title: Metabolic Inhibition of Anaplastic Thyroid Carcinoma (ATC)

This ThyCa grant is awarded in cooperation with the AAES.
 
Grant Recipient: Matthew A. Nehs M.D., F.A.C.S., Brigham and Women's Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts
 
Prior studies have shown that aggressive tumors like ATC have a very high rate of metabolism and glucose utilization. This can be seen clinically by PET scanning for tumor staging. ATC cells shift to using glucose as a primary fuel through glycolysis even in the presence of sufficient oxygen, as opposed to using the more efficient oxidative phosphorylation in mitochondria. This is called the Warburg effect and generally results in a high level of lactate production.

This research will investigate the role of energy metabolism in ATC cells. One method to target energy metabolism is by altering the diet composition to restrict glucose availability. Preliminary studies suggest that the ketogenic diet may be an important adjunct to standard therapies for anaplastic thyroid cancer. The ketogenic diet is a high-fat, moderate-protein and low-carbohydrate diet that restricts availability of glucose that can fuel tumor growth. Additionally, this research will investigate the role of lactate exporters to see if they can inhibit growth of ATC cells alone or in combination with the ketogenic diet. The research goal is to advance the knowledge of how diet and metabolism affect growth and treatments for the most aggressive and advanced thyroid carcinomas.
 
About Dr. Nehs. Dr. Nehs is an Endocrine Surgeon at Brigham and Women's Hospital and Dana-Farber Cancer Institute, and Assistant Professor of Surgery at Harvard Medical School. He is program director of the Harvard Combined Endocrine Surgery fellowship and associate program director for the General Surgery Residency at Brigham and Women's Hospital. He graduated from The University of Michigan Medical School. He completed further training at Brigham and Women's Hospital and at Massachusetts General Hospital, where he studied anaplastic thyroid cancer.