2025 Archives - Page 2 of 8

Hanna Mikkola, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Children with Down syndrome have a higher chance of getting blood cancer called leukemia. Many babies are born with a condition called transient abnormal myelopoiesis (TAM). TAM starts before birth and causes too many immature blood cells to grow. In most babies, TAM goes away on its own. But in some, it can be very serious or later turn into leukemia. Right now, doctors do not know why this happens or how to tell which babies are at risk.In this study, we will use new tools to look at single blood cells to learn more about how TAM starts, how it changes into leukemia, and why treatments sometimes stop working. We will study blood and bone marrow samples from children at different stages of the disease, as well as from pregnancies with Down syndrome, to find out when and where the first changes begin.Our goal is to find better ways to predict which babies with Down syndrome will get leukemia and to develop safer, more effective treatments. This work could improve survival and quality of life for children with Down syndrome and their families.

Raymond Moellering, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Burkett’s lymphoma and neuroblastoma are two different types of childhood cancers that share a common link: the MYC gene. Chemotherapy is often used for treatment, but the side effects can be hard on young patients. Doctors and researchers now know that the side effects are mostly from blocking the growth of both cancer cells and healthy cells. Chemotherapy also does not work well for some patients. Our research focuses on drugs that target MYC to safely slow the growth of cancer cells. We will test these new drugs in the laboratory for future development into medications for patients. In the end, our work will produce better medicines to treat these cancers without giving up patient comfort.

Chrysothemis Brown, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Cancer immunotherapy is a treatment that helps the body’s immune system fight cancer. It works very well for some cancers, but it is less effective in infants and children. One reason is that the young immune system is built to turn down strong reactions. This helps babies avoid harmful inflammation when they first eat food or meet the friendly bacteria in their gut. The Brown Lab recently found a new type of immune cell, called Thetis cells. These cells play an important role in suppressing immune responses during early life. We think they may also train the immune system not to attack cancers, which lets tumors grow. In this project, we will study how Thetis cells act in childhood cancers such as hepatoblastoma and use what we learn to design new treatments.

Uri Tabori, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

When the body is unable to fix damaged DNA, it can cause some childhood cancers to grow very quickly. These cancers have many DNA changes (called “mutations”) so we call them “hypermutant”. Some children are born with a syndrome, called CMMRD, which makes them develop a lot of these hypermutant cancers at a young age. A treatment called immunotherapy has shown positive results in these patients. However, it doesn’t work for everybody and when a cancer is found late, about 40% of children will get worse, even after treatment. Immunotherapy can also cause side effects, some of which are serious. Recently, we discovered that mRNA-LNP vaccines (similar to those used for COVID-19) may actually be able to prevent cancers in children with CMMRD. These vaccines have very few side effects and might help many patients. However, we still need to learn more about what components make an effective vaccine and then test it in human and animal models. In this project, we will do three things. We will first determine what should be included in a vaccine to make it work well. We will then test the vaccine in mice to see if it can prevent cancer. Finally, we will see how well the vaccine works and how safe it is for humans. To do this, we will work with international collaborators who have experience making vaccines. This work has the potential to help children with many other cancer-causing syndromes, as well as common adult cancers.

William Gwin III, MD

Funded by the Cancer Vaccine Coalition (CVC)

Over 310,000 people get breast cancer each year in the US. About 20% of breast cancers are caused by a protein called HER2 and are aggressive. We have developed a vaccine called WOKVAC that trains the immune system to identify and kill cancer cells that have high levels of HER2. Early results in patients show that the vaccine is safe and can create a cancer-killing immune system response. We are now conducting a patient trial where patients with HER2+ breast cancer get the vaccine along with their normal treatment before they have surgery to remove the tumor. Our goal is to have the vaccine create cancer-killing immune cells that will work together with their normal treatment to kill the cancer cells and protect the patient from the cancer for years or decades. So far, we have given the vaccine to 16 patients on this trial. The vaccine has been safe, and early results are encouraging. We are expanding the trial to 25 patients to better help us decide if other patients should get this vaccine. We are looking at how well the patients do after getting the vaccine and looking to see if the vaccine increases the number of cancer-killing cells in their tumors and blood.

Reshma Mahtani, DO

Funded by Hooters

This project is about helping young women, age 45 and under, who are diagnosed with breast cancer. These women often have more serious types of cancer and are diagnosed later than older women. We want to make it easier for them to learn about and join clinical trials. Clinical trials are studies that test new treatments to see if they work better than current ones.We want young women with breast cancer to get clear information and strong support when making choices about their care. Many are also dealing with big life events like having children, starting careers, or handling stress. These things can make it hard to think about joining a clinical trial. By adding a research assistant and training nurses to help, we hope to make the process easier and less confusing.This program will help young women feel more confident and informed about their treatment options. It will also help them learn about new therapies through clinical trials. By giving support and easy-to-read materials in both English and Spanish, we hope to improve their care and make their experience less stressful.

Alison Ringel, PhD

Immune therapy is a cancer treatment that turns on killer T cells to attack the tumor. It is a major advance in cancer care. As it is less damaging to healthy tissue than chemotherapy, it has fewer side effects. Most importantly, it can help patients with advanced disease who had few options before. However, many patients do not benefit from immune therapy. The reasons why are not fully understood. Cancer affects people of all ages, but it is much more common in the elderly. T cells are key to the success of immune therapy, but aged T cells do not work as well as young ones. We have discovered that a signal important for T cell function is lost as people age. The loss happens even before a tumor appears. As tumors grow, aging makes even more T cells lose this signal. Our research will test whether the loss of this signal explains why older patients do not respond to immune checkpoint therapies. We will explore ways to restore this signal to improve treatment outcomes. Through this research, we hope to make immune therapy effective for more patients, especially older adults who face the highest rates of cancer.

Anirban Das, MBBS, MD, DM

Funded by the Dick Vitale Pediatric Cancer Research Fund

Glioblastoma is a cancerous brain tumor and the major cause of cancer-related death in children, teens, and young adults. Standard treatments like surgery, chemotherapy, and radiation don’t work here. Our international consortium found a group of glioblastomas caused by problems with how DNA is copied. These are called replication repair deficient (RRD)-gliomas. We showed that they have many mutations and can respond after stimulating the body’s immune defenses using immunotherapy.We recently discovered three types of RRD-gliomas (RRD1-3). Each type acts differently and responds to treatment in its own way. We believe using specific treatments for each group will help patients live longer with fewer side effects. Our plans are:RRD1: These tumors have many immune cells. We will reduce use of harmful treatments like radiation.RRD2: These tumors have fewer immune cells. We will use two kinds of immunotherapy together to help the body fight the cancer.RRD3: These tumors have little immune activity. We will use immunotherapy with drugs that target special features of the tumor. These ideas are based on strong lab studies, tests in animals, and early results in patients. Now we will study how each tumor type responds differently to more precise treatments. We will track and adjust this in real time by testing tumor DNA in the fluid around the brain and spine. This project will advance research and improve care for young people with these deadly brain tumors. In the future, it will be expanded to help treat other types of deadly cancers.

Kenneth Westover, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Many children with cancer have changes in their genes that help tumors grow. One important change is called FGFR1 N546K, which is found in about 3% of children with solid tumors, including certain brain cancers and other childhood cancers. This change makes cancer cells grow faster, but current cancer drugs do not work well against it.Our research team will search for new medicines that specifically target this genetic change. We will begin by testing 65,000 compounds to find which ones block the cancer-causing protein. The most promising compounds will then be tested in cancer cells to confirm they work in the right way. Finally, we will study how these medicines attach to the protein using detailed imaging, which will guide us in improving them further.Children with this gene change currently have very few treatment options. If we are successful, the medicines we discover could help treat not only one type of cancer but many different childhood cancers that share similar gene changes. Our ultimate goal is to give doctors new tools that help children live longer, healthier lives and to create a path toward better treatments for childhood cancer.

Corinne Linardic, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Rhabdomyosarcoma (RMS) is a connective tissue cancer with features of skeletal muscle, and the most common soft tissue cancer of childhood. RMS can be classified as lacking or having a PAX3::FOXO1 fusion, in which part of the PAX3 protein becomes attached to part of the FOXO1 protein. This hybrid, fused protein is the driving mutation of fusion-positive RMS (FP-RMS). Survival for children with FP-RMS is less than 30%, and this has not improved in over 40 years. In fact, we have no new effective drugs for this cancer. Chemotherapies developed in the 1970s are still the best we have today. This research focuses on understanding how to block PAX3::FOXO1. However, PAX3::FOXO1 is a difficult drug target due to its complex structure. To complicate matters, at least six other fusions have recently been discovered that drive FP-RMS. Rather than being discouraged, we have leveraged this information. We have figured out that all of these seven fusions depend upon a core set of helper proteins to cause FP-RMS. In this project we will figure out the regions of the seven fusions that have common roles and that are responsible for recruiting the helper proteins. Last, we will use hi-tech chemistry to find small molecules to attach to these common regions to dissolve away the helper proteins. This will provide a platform from which to design, and in the future, clinically evaluate new drugs to block any fusion found in FP-RMS. We hope to provide targeted, less toxic treatments.