Funded by the Dick Vitale Pediatric Cancer Research Fund in memory of Colby Young
Children with changes in a pair of related genes (named DROSHA and DICER1) can get cancer in their lungs, muscles, kidneys, brains, and other organs. This is because DICER1 and DROSHA normally turn off pro-growth signals. When these pro-growth signals cannot be turned off, cancer can arise. We do not know which pro-growth signals are most important. Our lab found that one of these pro-growth signals, named Igf2, may be one of the most important. We came across this idea through studying mice that develop brain cancer due to Drosha changes. This project will study how important Igf2 is. It will also examine exactly how Igf2 gets turned on. Lastly, it will test whether a drug that targets Igf2 will be effective in these cancers.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Medulloblastoma is the most common brain tumor in children. While doctors can cure most of these children, the treatments are very toxic and negatively impact these patients and their families for the rest of their lives. Thus, scientists are trying to finding new therapies that are more effective and less toxic. A handful of new drugs have been tested in the last few years in patients with medulloblastoma. Most of these new drugs initially show great efficacy. Unfortunately, tumors rapidly become resistant and return more aggressively. Sadly, when these tumors come back there is no good treatment available and most of these children die. Therefore, it is very important to find drugs that can stop the growth of the tumors and prevent their reappearance. A series of experiments allowed us to find an ideal candidate therapeutic for children with medulloblastoma tumors. These compounds that target a family of proteins named BET, will reduce the size of the tumors and prevent them from growing back in the future. We believe that our research will provide a game-changing therapy for patients with medulloblastoma and restore hope in these children with cancer and their families.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Pediatric cancer patients have greatly benefited from advancements in CAR-T cell therapy, a cancer treatment in which a patient’s own T cells – a type of immune cell – are reprogrammed to recognize and kill cancer. CAR-T cell therapy has demonstrated remarkable clinical success and can even cure some patients; however, only 50% of those treated remain cured after 12 months. A major roadblock preventing this therapy from curing more patients is poor CAR-T cell survival. Patients with long-lived CAR-T cells are more likely to be cured than those with short-lived CAR-T cells. Therefore, there is an urgent need to develop strategies that help CAR-T cells stay in the fight against cancer.
My research project will test a new approach that helps CAR-T cells survive longer by tapping into the natural biology that helps T cells persist in the body. By forcing CAR-T cells to act more like naturally occurring long-lived T cells, we can boost their ability to survive and kill cancer. We will also determine the molecular “secret sauce” that allows some patients’ CAR-T cells to persist for longer compared to others. Collectively, this project will help advance more efficacious therapies for blood cancers and potentially other types of cancer in both children and adults, and reveal valuable information about CAR-T cell persistence that can be leveraged for future discoveries.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Children with aggressive brain tumors do poorly, and outcomes haven’t gotten much better for these terrible diseases in the past thirty years. A recent new treatment called chimeric antigen receptor (CAR) T cell therapy provides hope for these patients. CAR T cell therapy takes a patient’s own immune cells and reprograms them to find and kill cancer cells. We recently opened a unique Phase I clinical trial (NCT04510051) that uses CAR T cells to help children with hard-to-treat brain tumors.
We are excited that the first few patients treated on our trial had some shrinkage of their tumors. This gives us hope that CAR T treatment can help children with these diseases. Unfortunately, responses so far have been temporary, highlighting the clear and urgent need to improve these promising therapies. Our trial lets us sample cerebrospinal fluid repeatedly during treatment. This gives us a valuable chance to study in fine detail how CAR T cells talk to the patient’s immune system, and how that conversation changes over time. We know that if CAR T cells can teach the immune system to destroy tumor cells, treatment will work better. However, this does not happen very often in patients. Our study will help us figure out how to make CAR T cells that effectively promote an antitumor immune response, leading to better therapy for pediatric brain tumors with five years.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer
Brain and spine tumors are the leading cause of cancer-related death in children, adolescents, and young adults. Outcomes for pediatric and young adult patients diagnosed with high-grade gliomas (HGG) remain dismal, with 5-year overall survival tragically <10%, despite intensive surgery, radiation, and/or chemotherapy. There is therefore a critical need to develop effective, well-tolerated therapies for children and young adults with HGGs. Recent scientific discoveries have provided valuable insight into the genomics of these aggressive diseases and identified genetic changes which can serve as targets for therapy. Research has helped develop less toxic medicines, usually oral drugs, which can directly target specific genetic alterations present in the tumor to slow or stop its growth and spare healthy organs. We propose an innovative multi-arm clinical trial offering a precision medicine approach to treat children and young adults newly diagnosed with HGGs. Detailed genetic sequencing using advanced technology will be performed on tumor tissue from all patients upfront, with return of results within 3-4 weeks. Patients will then be assigned to one of several unique molecularly-targeted treatment arms based on (and directly targeting) the genetic alterations identified in their tumor. We will also collect blood samples as well as cerebrospinal fluid and/or future tumor tissue throughout the study. Genomic and immune profiling analyses will be performed on these specimens over time that, in combination with imaging and patient-survey measures, can predict early response or recurrence to treatment (“liquid biopsy” tools) and improve the understanding of why some tumors become resistant to therapy.
Black women have significantly higher breast cancer death rates compared to Non-Hispanic White women. This difference represents an important public health concern and an important target for the development of solutions. Cancer clinical trials are important in solving the differences that exist in cancer health care between Black and White patients, because they provide high-quality, guideline-driven health care. It is important to have clinical trial participants be similar to that of the general population, so that any development of new drugs or interventions from these clinical trials are effective for everyone in the population. Unfortunately, Black women are substantially underrepresented among cancer clinical trials. Consequently, given their lower participation, any positive outcomes from such trials may not be relevant to Black patients. If not corrected, this will lead to continued differences in cancer health care between Black and White patients. The most commonly identified barriers affecting participation in clinical trials among Blacks, include issues of trust, experimentation, poor communication, and access. These issues need to be addressed because, Black patients participate at similar rates compared with White patients when offered clinical trials and help with any barriers. We are part of the largest health system in the state of New Jersey and serve large populations of Black patients. We offer a variety of cancer clinical trials and we propose to put into action, a comprehensive program using patient navigators, patient advocates, marketing and communication, and physician engagement to increase awareness and participation of Black breast cancer patients in clinical trials.
Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Cancers are driven by mutations, or changes in the DNA that encode the proteins and processes that allow the cells in our body to function normally. Those mutations make proteins work differently, making cancer cells grow faster or live longer, but they also make cancer cells look different from normal cells to the immune system. This process is similar to when someone gets a viral infection, where viruses infect normal cells, and the immune system battles the infection by recognizing the infected cells by the presence of viral proteins.
There are a series of molecules, called the Human Leukocyte Antigens (HLAs), that are responsible for showing those foreign proteins to the immune system on the surface of the diseased cells. Cancer cells can also change or lose these HLAs, so that the immune system no longer sees the cancer cells as “different” from normal cells. My research is focused in understanding these HLA molecules in skin cancer, to address the question of how the cancer cells avoid getting killed by the immune system. Skin cancers are generally treated with therapies that help the immune system kill cancer cells, and my research helps us understand why these therapies may or may not work. By explaining whether HLAs are different in cancer cells, my research may improve the success of our treatment strategies in skin cancer.
North Carolina (NC) has the largest American Indian population east of the Mississippi River. Yet, we do not know much about the health and health care of NC American Indians. Because cancer is the number one cause of death in NC American Indians, we need to better understand cancer and cancer-related needs in this unique population in order to reduce the cancer burden. Three NC cancer centers joined together in 2021 to partner and learn more about how to help American Indians with cancer. We also want to find and develop community resources for American Indians with cancer in North Carolina.
In this study, we will explore how cancer affects American Indians in North Carolina. First, we will measure the number of cancer diagnoses and deaths from 2003-2019. We will also learn more about how and where American Indians receive cancer care. These data will come from the North Carolina Cancer Registry and health insurance files. Second, we will ask tribal leaders to help us explore the needs and barriers to healthcare in American Indian communities. Finally, we will work with American Indian youth leaders to understand tribal community strengths and local resources that can help with cancer care.
This information will help American Indians by showing where the greatest needs lie and pointing to opportunities for better care, with a long-term goal of improving cancer outcomes in all American Indians.
Funded in Collaboration with the University of Florida Foundation
Brain cancer is now the leading cause of cancer-related death in children, due to the significant improvements in outcomes for children with more common cancers such as leukemia. This research proposal advances a novel immunotherapy treatment for medulloblastoma (MB), the most common malignant brain tumor in children. We have pioneered a treatment platform for pediatric brain tumors called adoptive cellular immunotherapy, which involves expanding tumor-reactive ‘killer T cells’ to large numbers outside of a patient and delivering these potent immune cells back to children with resistant brain tumors. This approach is currently undergoing evaluation in first-in-human clinical trials at our center. This project will advance this platform into a next generation approach that uses genomic technology to identify patient-specific antigens expressed in medulloblastoma tumors and specifically isolate and expand T cells recognizing these unique tumor targets (called neoantigens). If the objectives of this study are met, we will be able to significantly enhance the specificity and potency of an already promising platform and rapidly translate our findings into innovative clinical trials for children battling brain cancer.
