Gelareh Zadeh, MD, PhD, FRCS(C)

Funded by Hockey Fights Cancer™ Powered by the V Foundation

Meningiomas are the most common intracranial tumor in adults. While most meningiomas can be successfully treated with surgery, there are a significant proportion of cases that require the addition of radiation therapy to delay tumor recurrence. However, our current methods of selecting which patients should be escalated for radiation after surgery remain relatively imprecise, especially for intermediate-grade meningiomas that can behave in a highly variable manner. Molecular profiling, specifically DNA methylation of meningiomas has proven to be an effective and efficient method of providing additional information on these tumors that can be used to better predict whether they will or will not recur after surgery. However, whether a similar set of molecular signatures exist to predict whether a meningioma of any given patient will respond to radiotherapy after surgery remain to be determined. This V Foundation grant will enable us to 1) develop a clinically important predictor using specific molecular signatures of any given patient’s meningioma to tell us whether their tumor will respond to radiation, 2) test this predictor through a novel, real-time, molecular-pathology informed clinical trial, and 3) determine if the same signatures that can prediction response to radiotherapy in the tumor tissue can be used to non-invasively provide the same information through a simple blood test. Results from this study have the potential to dramatically improve the way we treat patients with meningiomas and will represent a significant shift forward in the field of neuro-oncology.

Kathryn Weaver, PhD

Funded by the 2022 Victory Ride to Cure Cancer

Cancer care can be tough to navigate. Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFBCCC) wants to make sure all patients can access the best cancer care as easily as possible. Sometimes the best treatment outcomes are achieved by joining cancer research studies. To be sure treatments studied in cancer research are reliable and consistent for all patients, it is important that all groups are represented. African Americans have the highest percentage of new cancer cases in the U.S. and the worst outcomes, yet are less likely to be represented in research. Due to language and cultural barriers, Hispanic patients also have low research participation rates. Adolescents and Young Adults have the lowest research participation rate of any age group. It can also be harder for patients who live outside of the city to get cancer treatment because of where they live. To help ensure all groups are included in studies, AHWFBCCC created a population health navigator (PHN) program to help community members learn about cancer, how to prevent it, what screening is required, and what treatments are available. If someone is diagnosed with cancer, the PHN can help to remove barriers to care and help patients learn about the benefits of cancer research. With PHNs, AHWFBCCC hopes to increase research participation so that all can be represented.

Asmin Tulpule, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

We study a set of bone cancers that affect children and young adults. The treatment for these cancers has remained the same for the last 40 years – combinations of toxic medicines known as chemotherapy, followed by surgery or radiation to remove what is left of the cancer. While this strategy cures some patients, far too many children continue to die from these cancers. We believe we have found two specific weaknesses in these tumors: problems in their ability to repair damage to their DNA and a survival signal in a special pool of cancer cells known as “residual disease”. Through this research, we hope to bring new therapies to patients and cure more children with these bone tumors.

Joelle Straehla, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

One major challenge in treating any type of cancer is resistance, or when a cancer stops responding to a certain type of drug or therapy. Some cancer cells may become resistant my changing the way they read and write their DNA, or the genetic blueprint in the cell nucleus. Other cells may change the way proteins are expressed on the surface, which can change their shape or ‘stickiness’ and ability to move in the body.  When doctors can understand exactly how cancer cells become resistant to a certain drug, they can sometimes combine two or more drugs together to overcome this.

For some new classes of drugs, we have not even begun to explore how cancer cells might become resistant. One of these classes is nanoparticle drugs, which usually involves bringing together molecules like fats or polymers to help delivery drugs into certain cells. The goal of this research project is to identify the ways that pediatric cancer cells can become resistant to nanoparticle drugs, and find new drug combinations that are more effective and less toxic to children with cancer. Many lab-based studies of nanoparticles are performed in common cancers of adulthood such as breast cancer, and this has led to new treatments in the clinic, but there have been very few studies of nanoparticle drugs in childhood cancer. Currently, there is only one nanoparticle drug approved for use in children. By studying resistance to nanoparticle drugs in a deadly childhood brain tumor, we can take the first step towards a new clinical treatment for these children.

Eric Rellinger, M.D.

Funded by the Dick Vitale Pediatric Cancer Research Fund

Neuroblastoma is a childhood cancer that develops from nerves outside of the brain. Half of these cancers spread and cause high rates of death despite treatment. Many researchers study how proteins impact cancer growth and spread. Proteins work differently when sugars are attached to them. Sugars are added to proteins through a process called glycosylation, and the way that sugars are added is different in adult cancers. Few people have studied how glycosylation changes the behavior of childhood cancers. We have applied new technology to studying neuroblastomas and found that a certain sugar, fucose, is decreased in advanced tumors. We will extend our work and look at how sugars change when cancer cells are treated with chemotherapy. We found that decreased levels of fucose increases the ability of certain immune cells to find neuroblastoma cells. We have proposed studies to determine how proteins joined to fucose change how neuroblastomas are recognized by white blood cells. The proposed work will be the first use of this technology to define how cancers cells change their sugar patterns to avoid death when treated with chemotherapy.

Reshma Mahtani, DO

Funded by Hooters

Our research project focuses on improving the lives of women battling breast cancer by increasing their participation in clinical trials. Clinical trials are studies that help us find better ways to treat cancer. Right now, breast cancer is a big concern, especially for Black and Hispanic women. We want to change that.

We plan to host special events in South Florida where women can learn about clinical trials in a simple way. We will have experts talking about what clinical trials are, who can join, and what the benefits and drawbacks might be. These events will be in different counties like Miami-Dade, Broward, and Palm Beach. We know each place has its own challenges and needs, so we’re adapting our approach to help as many women as possible.

Not many women join clinical trials, which means we don’t learn enough about new treatments. Our project aims to change this by reaching out to communities and making sure everyone has the right information. We especially want to help women from backgrounds that haven’t had many chances to be part of research.

Our goal is to make these events easy to understand and welcoming. We’ll even provide information in Spanish for our Hispanic community. By doing this, we hope to inspire more women to join clinical trials. The research we do together could lead to better treatments and better chances of beating breast cancer. We’re excited about the possibility of helping more women survive and feel better during their fight against cancer.

Xiao-Nan Li, M.D., Ph.D.

Funded by the Dick Vitale Pediatric Cancer Research Fund

Clinical outcomes in children diagnosed with high grade glioma and diffuse intrinsic pontine glioma remain very poor. Even with surgical resection, chemotherapy and radiation, most of the tumors eventually relapse.  This is primarily because some cancer cells develop resistant to the therapies that doctors prescribe. For the past 50 years, the identities of these therapy-resistant cancer cells remain unknown. Difficulties of obtaining relapsed tumor tissues and limited availability of animal models are the major reasons why we still don’t have new treatment. With the strong support of patients and families, we have developed a panel of animal models by directly implanting brain tumor cells into the brains of immunodeficient mice. We can now use these models to mimic what happens in children but treating the animals with the similar drugs/radiations. These models are very helpful. Indeed, our preliminary study in a small number of models have identified a set of cells expression CD57 as candidate root cells as they were found before drug treatment, remain present after very extensive clinical treatment, and can even survive the most harmful environment with no oxygen and no nutrient. This exciting finding has promoted us to perform a detailed analysis using more animal models to confirm the extraordinary capacity of the CD57+ cells in resisting therapy induced cell king, to understand how they can survive current treatment, and to find new drugs and strategies to selectively kill these seed cells. Our ultimate goal is to find new cure for children with highly malignant gliomas.

David Langenau, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Children with muscle cancer commonly develop resistance to therapy.  This is a major problem and most kids will die from resistant disease.   Our group has developed a new combination of drugs to kill muscle cancers and is now being tested in kids and young adults.   Yet, drug resistance to this same combination has been reported in other cancers and may develop in our patients. Our work will uncover how resistance develops and identify a new drug that can restore sensitivity to chemotherapy.  This work is important because the new drugs we identify could be used to treat kids in the future.

Daniel Herranz, PharmD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Acute Lymphoblastic Leukemia (ALL) is a common cancer in kids. There are two types, B-ALL and T-ALL, depending on the type of white blood cells affected. Most kids get better with current treatments, but sometimes the cancer comes back and we can’t help them anymore. That’s why we need new treatments for T-ALL.

We know that certain drugs used in the hospital affect how leukemia metabolism works. So, we wondered if changing the diet could also help. In our lab, we tried different diets on mice with leukemia. Surprisingly, we found that removing just one component of the food (an amino acid), made a big difference. Leukemic mice eating food without this amino acid lived much longer.
Now we want to understand why this dietary approach helps and if we can use it in combination with other treatments. We will study mice with leukemia and samples from real patients to see how this amino acid affects cancer. We also want to find out if combining this diet with current treatments works even better.

If our research is successful, we can try it on real patients. We want to see if reducing this amino acid in the diet can make treatments safer and help more kids survive, especially those whose cancer has come back. This research is important because it could give us new ways to treat leukemia and help more kids get better. It might even help with other types of cancer too.

Madeline Hayes, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Neuroblastoma (NB) is a type of childhood cancer that is difficult to treat after it has spread throughout the body. Using animals that develop aggressive NB, we found different types of tumor cells that may lead to cancer spread. We are proposing to look very closely at these different tumor cells and determine how they may lead to NB spread and drug resistance in patients. We will also test new targeted drugs for their effects on NB spread and through our studies, new ways to treat aggressive childhood cancer may be found.

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