Research studies that test how new cancer drugs work often don’t include all members of the United States population. Scientists are unable to tell how well these new treatments work in diverse groups. Our team will study how Black cancer patients and their families decide whether participating in a research study is right for them. We will talk with Black cancer patients and their families, doctors, cancer support groups, and Black community members to help us develop a public service video about clinical trials. We will also develop a plan to share information about clinical trials among Black communities. This approach will help us develop a public service video that is based on the needs, experiences, and strengths of Black communities that can be shared widely.
Funded by the Dick Vitale Pediatric Cancer Research Fund
The Schwartz Lab studies two genes, SAMD9 and SAMD9L that are known to cause a bone marrow failure syndrome in children called myelodysplastic syndrome (MDS). There are no reliable pediatric MDS model systems, thus we have created one from a special type of stem cell that contains mutated SAMD9 or SAMD9L. It is important to have these new cell lines, because cells that we can obtain from patients do not grow well or for a long time making studying them very hard. We will perform several tests in our new model system to determine why mutations in SAMD9 and SAMD9L cause blood stem cells to die. Together with our cell lines we have also developed a second set of tools that will allow us to turn on or to turn off SAMD9 or SAMD9L without using interferon—an inflammatory substance in the cell that turns on many other cell processes including SAMD9 and SAMD9L. We have completed initial experiments that suggest that SAMD9 and SAMD9L are important in how cells communicate during inflammation and other immune responses. Our proposed experiments will further determine how disease-causing mutations in SAMD9 and SAMD9L disrupt communication in these important cellular pathways. Understanding how SAMD9/9L mutations effect the blood stem cells will help us determine the right treatment approach for patients with pediatric MDS, because some patients with SAMD9 or SAMD9L mutations may not need treatment at all.
Funded by the Dick Vitale Pediatric Cancer Research Fund and the V Foundation Wine Celebration in honor of Bob McClenahan
Leukemia is a blood cancer that can be fully treated with anti-cancer drugs in most people. However, many people with leukemia do not respond to these drugs and are at risk of dying. It is not known why some leukemias respond to treatment while others do not. We believe that the type of normal blood cell that becomes leukemic impacts the behavior of individual leukemias. We believe that if a normal blood cell possessing the ability to form many other types of blood cells (in other words, it is a blood ‘stem cell’) turns into leukemia, this leukemia will be hard to treat. On the other hand, if the normal blood cell does not possess such properties – it is a more mature blood cell – this leads to treatable leukemia. In this proposal, we will apply our experience in engineering different types of blood cells (stem cells and more mature blood cells) to become leukemic. We will ask how the type of healthy blood cell impacts the behavior of the resulting leukemia. We will use genetics to understand how the properties of normal blood stem cells are transferred to leukemia cells to impact aggressiveness. We expect that successful completion of this study will improve our understanding as to why some forms of leukemia are treatable and why some are not treatable. We hope that these conclusions can lead to better understanding of individual patient leukemias and improved treatments.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Rudd Foundation in memory of Leslie Rudd
Immunotherapy is a type of cancer treatment that boosts the body’s immune system so that it can fight the cancer. Whilst this type of treatment has proven very successful for certain cancers in adult patients, this approach has been much less effective for the treatment of cancer in children. One reason for this is that the immune system of children is very different from adults and may not respond to treatments designed to target adult immune cells. Remarkably little is known about the cell types in children that suppress anti-cancer immune responses. The Brown Lab recently discovered a new type of immune cell —Thetis cells — that may be pivotal in reducing the efficacy of immunotherapy in the very young. We hypothesize that Thetis cells help to “train” T cells not to attack the body’s own normal cells, and in so doing creates an immune environment that also tolerates malignant tumors. In this project, the Brown Lab seeks to reveal, on the molecular level, how Thetis cells work and thus how to create immune therapies for children while not provoking auto-immune diseases that overactive T cells sometimes cause.
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
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.
