Funded in partnership with Miami Dolphins Foundation
Sarcomas are cancers of the bone and muscles, often seen in children and young adults, which are very hard to treat with very few patients surviving. Our aim is to improve treatment options for these patients. A vaccine trial using patient’s dendritic cells which are a type of immune cells, modified to identify and attack the individualized cancer was conducted at Sylvester comprehensive cancer center in 2019. Surprisingly, we noted good response in a few patients, who remain cancer free over 2 years from receiving the vaccine treatment. Therefore, the aim of this research proposal is to study the immune/non-immune cells of the surgically removed tumors and blood of patients treated on this trial. Using special high-resolution imaging methods in which key immune markers are tagged in the tissue, we will describe the immune cells in each patient’s cancer environment and correlate these to whether the patient did or did not respond to the cancer vaccine. We will also measure key immune cells in the blood of these patients collected after vaccine treatment and compare this with response to the vaccine. These detailed immune studies on patient tissue and blood samples will then guide future anti-sarcoma cancer vaccines and potential immune cell therapy to cure these aggressive cancers.
Breast cancer is the most common cancer in women in the United States and second leading cause of cancer death. When a woman is diagnosed with metastatic breast cancer (MBC) (cancer that has spread to other parts of the body) she has a less than 30% chance of surviving 5 years. These statistics remain despite decades of research and many new treatments for MBC. This suggests that we need better ways to administer drugs for MBC.
Hormone receptor positive (HR+) breast cancer is fed or fueled by estrogen and progesterone, the natural hormones of the body. HR+ MBC is initially treated with drugs that block the estrogen and progesterone production in the body. However, eventually cancer cells can become “resistant” to these hormone blocker drugs, most commonly by developing a “mutation” in the receptor of estrogen called ESR1. Once this mutation develops, the treatment is more challenging and usually involves use of chemotherapy which can lead to patients feeling sick and having multiple side effects from treatment.
In this proposal we plan to enroll HR+ MBC patients who have already developed an ESR1 mutation and offer a novel way of targeting this mutation. This will help extend time on treatment with minor side effects and possibly increase survival. We will do so by creating vaccines out of their own immune system that will allow them to wake up and engage in the fight against their cancer. This treatment will be combined with standard of care hormone blocking therapy.
North Carolina (NC) has the largest American Indian population east of the Mississippi River. Many American Indians in NC smoke cigarettes, which can lead to lung cancer. Yet, we do not know much about the needs of NC American Indians related to tobacco use and lung cancer. Three NC cancer centers joined together in 2021 to learn more about how to help American Indians improve cancer outcomes. In this study, we will first explore how often American Indians use treatment to help them quit tobacco. We will also explore whether they have been screened for lung cancer and what cancer treatments they receive. Second, we will ask American Indian community members about quitting tobacco, lung cancer screening, and their healthcare. Finally, we will work with American Indian community members to modify a quit smoking program to make it more relevant to them. We will also work with them to modify materials that tell people about lung cancer screening. This information will help American Indians by helping them quit tobacco and detect lung cancer sooner, which will help improve the health of American Indians in NC.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Diffuse midline glioma (DMG) is a fatal pediatric brain tumor, striking 200-400 children in the U.S. each year. Most children with DMG survive <1 year and have no proven therapies beyond radiation. A series of new drugs are being tested in clinical trials of DMG patients, but we lack sufficient tools to track how well they work. Cancer is a rapidly moving target as it can mutate to evade the onslaught of anti-cancer drugs; thus, tumors must be analyzed repeatedly during treatment to assess therapy response. Today’s standard of care for DMG is limited to frequent imaging (MRI), which provides insufficient data to assess therapeutic response. By advancing a new blood-based assay specific to DMG, we aim to dramatically improve our ability to track the effects of treatment on this devastating disease. We will exploit extracellular vesicles (EVs) — small “bubbles” shed by cells — as surrogate markers of therapy response in DMG patients. EVs contain molecular contents (e.g., protein, RNA, DNA) from their mother cells. Tumors shed large quantities of EVs into the bloodstream, offering a potential new way to monitor treatment in DMG patients. We will develop a new assay platform that integrates cutting-edge developments in materials, optics, and deep learning AI into a single system for efficient EV analysis and test whether our platform reliably predicts drug response in DMG patients. Our approach has the potential to transform DMG therapeutic trials and clinical practice, and its flexibility may lend itself to other types of pediatric and adult cancers.
Funded by the Dick Vitale Pediatric Cancer Research Fund in honor of Beau Christensen
Primary brain tumors are the most common solid tumors in children. They are also the most frequent cause of cancer-related death in children and teens. Genetic profiling is an important tool in the treatment of these tumors. DNA sequencing provides information for proper diagnosis. It can also be used to understand how tumors change over time and to monitor response to treatment. However, performing biopsies is very challenging for brain tumors. Many tumors are in important areas of the brain and can’t be fully removed or repeatedly sampled.
“Liquid biopsy” is a new tool that can be used to diagnose cancer and track response for some systemic tumors. It works by detecting small pieces of DNA that break off from tumors. These can be found in the cerebrospinal fluid (CSF) and in blood (circulating tumor DNA, ctDNA). Accessing these “liquids” is usually easier and has fewer complications than surgery.
We previously showed that CSF ctDNA can be used to diagnose brain tumors and that ctDNA is associated with active disease. But there are instances where CSF ctDNA is not informative due to technical limitations. We propose to improve how these samples are analyzed so CSF liquid biopsies can help more patients. Our prior work was retrospective. For this project, CSF ctDNA monitoring will be added to a clinical trial. We will investigate whether there is a relationship between CSF ctDNA and disease burden. Validating CSF liquid biopsy could greatly improve how pediatric primary brain tumors are diagnosed and treated.
Funded by the Dick Vitale Pediatric Cancer Research Fund
The bone cancers Ewing sarcoma and osteosarcoma are some of the most common solid tumors occurring in children and young adults. When these tumors spread outside the bone where they start (metastatic disease) or they come back after initially going away (relapse), they are very aggressive and nearly impossible to cure. New treatments are urgently needed. CAR T cells are a type of therapy that uses a patient’s immune system to attack their cancer by recognizing a target on its surface. This target must be minimally expressed on normal cells to prevent toxicity. We have identified a target B7-H3 as being highly expressed on Ewing sarcoma and osteosarcoma and will now run a clinical trial testing antiB7-H3 CAR T cells in those diseases. We will also re-engineer these CAR T cells to be more effective in potential future trials.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Glover and Frazier families
T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) are types of blood cancer that are very hard to treat. Patients with these leukemias need to get strong chemotherapy that can have bad side effects. Because of this, we need to find new treatments that are less toxic. CAR T-cell therapy is a new type of treatment that uses the patient’s own white blood cells and allows them to detect and kill cancer cells. These therapies can focus on only killing the cancer cells and not normal tissues and have few side effects. We have invented a way to treat this type of leukemias and have shown that it works well in models in the laboratory. We want to find out if our CAR T-cells are safe and effective in patients with childhood T-ALL/LBL. To help us reach our goal, we have formed a group of experts, including a) Lab experts – who design CAR T-cells, b) Clinical experts -who know how to treat leukemias c) Immunology experts – who can tell us how the CAR T-cells work and d) Pathology experts – who can study how the leukemias respond to the treatment. Our hospital has what is needed to start the clinical trial that we are planning. We want to find a cure for T-ALL/LBL that has few side effects and help save the lives of children with this type of leukemia.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Osteosarcoma is the most common bone cancer of children. When this cancer recurs in the lungs, we have no effective therapies for these patients, and they continue to be treated with the same drugs that have been used for the past 40 years. This work seeks to develop new treatment options for patients with recurrent osteosarcoma. We will use dogs, a natural model of this cancer, to test a new drug combination which uses the immune system to stop osteosarcoma growth. We will also use advanced monitoring techniques to determine which patients benefit from this new treatment. Testing these drugs in dogs will inform how best to use these new therapies for human patients with osteosarcoma. Importantly, it uses drugs which are also readily able to be used in human patients, thus having the potential for rapid movement to the clinic.
Black patients are more likely to die from breast, prostate, lung, and colorectal cancers than White patients. There are many reasons for these differences, including difficulty receiving life-saving treatment. New treatments that match the type of cancer a patient has to specific drugs have been developed and has changed the way we treat the disease. The first step to getting these new treatments is for patient’s tumors to be tested for specific changes. However, Black patients are less likely to receive these tests and to receive the relevant treatment. If progress is not made in improving access to testing, Black patients will continue to have lower access to these lifesaving treatments, causing even bigger differences in survival. In this study, we will develop a program to understand the needs of Black cancer patients and provide support to ensure that they receive appropriate tests and treatment. To help design the program, we will interview Black patients and healthcare providers on what the needs are and provide navigation support to patients. We will measure how effective the program is in increasing testing and treatment among Black patients. In the future, we hope to use this data to develop broader strategies that will improve Black patients’ access to tests, clinical trials, and treatment.
Funded by Kay Yow Cancer Fund 2023 Final Four Research Award
One of the greatest challenges in cancer treatment is that response to standard treatment is frequently incomplete and causes many side effects. Current treatments are often ineffective because they function as a “one-size-fits-all” approach to a very personal disease. This lack of success is magnified in triple negative breast cancer (TNBC), which differs greatly between each individual. We have recently discovered a protein that is not expressed anywhere in females, except in TNBC tumors, where it is required for tumor growth. This protein is normally only found in male testes. Thus, this protein is a perfect target to inhibit tumor growth without impacting normal tissues. Here we will study the function of ZNF165 and determine how it promotes growth of tumors. Ultimately, this work could lead to a tailored approach for treating TNBC without harming the patient.
