Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer
Despite significant advances in the treatment of pediatric cancer, leukemia remains the second leading cause of cancer related death in children. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that affects both children and adults. When T-ALL does not respond to chemotherapy or returns after initial treatment (relapses), there are few treatment options. New treatments are needed for T-ALL. The way cancer cells use energy or develop building blocks for growth is different from normal cells. We are working to understand how these energy and building processes within T-ALL cells are altered, with the hope that we can use this as a vulnerability for developing new therapies. We are particularly interested in drugs that alter how the cells produce a building block called methionine, and we are testing how these drugs work in T-ALL. Our ultimate goal is to find effective and non-toxic treatments for T-ALL.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Childhood brain tumors are a major cause of death for children. Medulloblastoma is one of the most common brain cancers in children and also one of the most difficult to treat. These children typically need extensive surgery, chemotherapy, and other treatments. Unfortunately, even with these treatments, many children with this cancer die from their disease. I am a pediatric neuro-oncologist, and it is my career hope to bring new therapies for medulloblastoma from the lab into the clinic.
My research studies why some children with medulloblastoma do not respond to treatment. I have made several discoveries that point toward new biology within the cancer cells that promote its growth. I have particularly focused on a new category of genes that we have recently described, called microproteins. These are small proteins that were missed in prior research on this cancer, and we have found that they are important for the ability for cancer cells to survive. I am optimistic that these discoveries are pointing towards new treatment options. To grow this vision, this V Foundation award will allow me to focus on studying certain new genes that we hope will lead to new treatments. Through this work, I hope to make new discoveries in medulloblastoma that are important for patients.
We are trying to find out why some ovarian cancer patients don’t respond to chemotherapy. Even though many patients start off well with the treatment, most eventually become resistant to it. When that happens, the only option left is to focus on making the patient comfortable, not curing the cancer.
To solve this problem, we need to understand what causes this resistance so we can develop new treatments. In our study, we found an important factor linked to this resistance by looking at patient data. Early tests suggest this factor might affect immune cells and cause resistance. We will investigate how this factor works and test new ideas using animals, patient samples, and state-of-the-art technologies.
Glioblastoma is a fast-growing and deadly brain cancer. Current treatments, like brain surgery, chemotherapy, and radiation, help, but most patients live for only about one year. Older patients with glioblastoma tend to do worse than younger patients, but we do not fully understand why. We believe that changes in the brain as people get older might help the cancer grow faster. Our project will explore whether changes in a part of the brain called white matter make it easier for glioblastoma to grow in older patients. Studying this in humans is difficult because it’s not safe to measure these changes in the brain while a patient is alive. To solve this, we will study mice, which have brains that change in similar ways as they age. We will examine whether tumors grow in the white matter more often in older mice compared to younger ones and try to identify the cells that allow this growth. To confirm our results, we will also study the white matter of human patients who died from glioblastoma to check if older patients are more likely to develop tumors in this area. The results from our study will help explain why glioblastoma is worse in older patients. This knowledge could help us find new treatments that slow tumor growth and help patients live longer.
Immunotherapy works by boosting the immune system to attack cancer cells and has improved the survival of many patients. An increasing number of cancer patients are now receiving immunotherapy, but there is no reliable way to predict who would have a good response. In addition, patients can experience a common side effect of immunotherapy, when the activated immune system attacks healthy organs, known as immune-related adverse events (irAEs). These side effects are often hard to diagnose until they have caused significant organ damage and can be life-threatening if not treated promptly. We have developed a new method, MethylSaferSeqS, that can provide an accurate measurement of the amount of remaining cancer in the body and detect early irAEs – all with a single blood test. MethylSaferSeqS can be applied to improve the care of cancer patients in several ways. First, it provides an early readout of treatment response and can identify the patients for whom immunotherapy is not working. These patients should be promptly switched to another therapy that could be more effective. Second, an accurate measurement of the remaining tumor in the body after completion of immunotherapy can identify the patients who should undergo additional treatments, such as surgery or chemotherapy, that would improve their chance of a cure. Lastly, an early detection of irAEs will allow timely treatments before serious damage is done to healthy organs. We will apply MethylSaferSeqS to samples collected from colorectal cancer patients who are receiving immunotherapy to test these goals.
Funded by the V Foundation’s 30th Anniversary Gala Event
Pancreatic cancer is the 4th most common cause of cancer death in the United States with one of the worst survival rates of any cancer. Patients with pancreatic cancer struggle to find clinical trials given the lack of options, the lack of any promising findings, the lack of functionality to tolerate many trials. Our research directly impacts cancer patients providing an innovative and promising therapy that has had success in other cancers. Our clinical trial will study pancreatic cancer patients receiving treatment with their own immune cells that we will have taken from their blood, re-engineered the cells to fight their cancer, and injected their re-engineered immune cells back into their body.Our research will study the blood from these patients and look for markers that are associated with treatment response in similar clinical trials. We will also study their tumor tissue before and after treatment and look to see if the injected, re-engineered immune cells were able to travel to the tumor, grow and thrives and kill cancer cells.
Funded by the V Foundation’s 30th Anniversary Gala Event
There is a new kind of cancer treatment called immune checkpoint blockade (ICB) that helps the body fight cancer by making the immune system stronger. Doctors use ICB with chemotherapy to treat triple-negative breast cancer (TNBC), but it doesn’t always work for everyone, so we need to find better ways to help these patients.
Scientists are studying tiny living things called microorganisms, like bacteria, that live in and on our bodies. These microorganisms can help us stay healthy and fight diseases. New research suggests that the gut microbiome—the collection of microorganisms in the digestive tract—might influence how well these treatments work. Some types of bacteria can help people respond better to the ICB treatment because they release beneficial metabolites.
In this project, scientists want to see if probiotics (which are good bacteria) or the beneficial metabolites they make can make the cancer treatment work better. They will look at samples from patients before and after treatment to see if these good bacteria and metabolites are helping.
There is a need for new treatments that increase survival for advanced prostate cancer (PC) patients. Doctors mostly still rely upon hormone therapies for PC, but patients become resistant to these drugs. Sometimes this resistance occurs through developing neuroendocrine (NE) PC. This change is controlled by enzymes that regulate the gene expression programs. Many patients have mixed tumors with both forms of PC. Unfortunately, such patients have poor clinical outcomes. Therefore, it is important to identify drugs that can treat both to increase patient survival. One approach is to target lysine-specific demethylase 1 (LSD1), one of the key enzymes needed for NEPC transformation. In this study, we will be using tumor tissue from PC patients treated with a drug targeting LSD1. This will help to identify patients that will benefit from this treatment and better direct patient selection in future clinical trials.
Funded by the V Foundation’s 30th Anniversary Gala Event
Despite its exciting impact, most cancer patients still do not benefit from immunotherapy. We have discovered a strategy used by cancers to avoid detection by the immune system. This work aims to use markers to determine which patients would be more likely to benefit from blocking this pathway in order to improve the effectiveness of immunotherapy. Using such a tailored approach is expected to enhance responses in a greater number of patients while avoiding the use and costs of ineffective therapies.
Funded by the V Foundation’s 30th Anniversary Gala Event
About half of all cancer patients will get radiation therapy (RT) as part of their treatment. But some cancers are naturally resistant to RT, and others become resistant over time. One idea to fight this resistance is to combine RT with treatments that boost the body’s immune response. In this project, we will test if a particular type of immunotherapy can overcome resistance to radiation and make RT work better. To check this idea, we’ll start by using lab mice to figure out the best way to do this treatment. These mouse tests will show us when to give the immunotherapy with RT for the best results. Once we know this, we’ll start a clinical trial with pet dogs that have cancer. The goals of this trial are to (1) prove that combining localized immunotherapy with standard RT is safe, and (2) show that this mix works better than just RT alone. The specific immunotherapy we’re looking at is called XCSgel-IL12. It’s a new type of treatment we made. It gets injected straight into the tumor, and it can be made in large amounts for a low cost. It looks very promising for beating radioresistance in many cancer types. This study will focus on soft tissue sarcoma. If it works well, we can start trials in humans with this type of cancer. It could also spark more research on combining RT with XCSgel-IL12 in other cancers in the future.
