Grant Archive - Page 4 of 141

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.

John Mullinax, MD

Funded by Jeffrey Vinik and the Tampa Bay Lightning in support of Hockey Fights Cancer powered by the V Foundation

White blood cells in the body are responsible for fighting disease. The disease is usually infection but the immune system can also kill the tumor in a patient with cancer. There are new forms of treatment called “immunotherapy” which increase the immune response to a tumor in a patient with cancer. This proposal is based on treatment using the white blood cells that reside within a tumor. Because they live within the tumor, they recognize the tumor as foreign, but the tumor defends itself from these cells. To tip the balance in favor of the immune system, these cells are grown outside of the body, away from the harmful effects of the tumor. They are then given back to the patient and since they are stronger, they can more easily kill the tumor. An ongoing clinical trial is testing the treatment in pediatric patients. In this proposal we will evaluate the cells that are given to these patients so we can better understand how they work and improve the treatment for future patients.

Sima Ehsani Chimeh, MD

Funded by Hooters

Breast cancer is the most common cancer in women. In about one out of three cases, the cancer spreads to other parts of the body. One type, called HER2-positive breast cancer, often grows faster and is harder to treat when it spreads. Current treatments have helped many people, but they do not always work and can cause serious side effects.Our project is creating a new way to both find and treat HER2-positive breast cancer. We are developing a medicine that can deliver tiny amounts of radiation straight to cancer cells. Depending on the type of radiation used, the medicine can either help doctors see the cancer with a scan or destroy it.It works like a “smart missile.” First, it can locate the cancer in the body with a special imaging test. Then, it can carry a different type of radiation to the tumor to kill the cancer cells, while leaving most healthy cells unharmed.We believe this approach could help doctors choose the right treatment for each patient, lower the chance that the cancer will come back, and cause fewer side effects than treatments like chemotherapy. If successful, this strategy could improve both the length and quality of life for people with HER2-positive breast cancer.

Augusto Faria Andrade, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund and the Dick Vitale Pediatric Cancer Research Fund

Some brain tumours in children grow very quickly and are hard to treat. As a result, many children affected by these tumours have poor outcomes. Scientists know that changes in the DNA of tumour cells help them grow, but they are still learning how these tumour cells interact with the body’s immune system. Tumour cells are surrounded by immune cells, which can sometimes help the body fight the cancer, but in other cases, they may help the tumour grow. Researchers have worked for years to help the immune system find and kill cancer cells. While this approach has worked well for some types of cancer, it has not been effective in treating paediatric brain tumours. By studying the tumour and immune cells together, we hope to identify which types of immune cells are present, what they do, and how they interact with brain and tumour cells. Our study aims to learn how immune cells act around these tumours and how we might be able to change their behaviour to help fight the cancer. We will test whether blocking specific cell communications can help slow down tumour growth and train the immune system to recognise and attack the cancer. What we learn here could lead to new treatments that help children with these serious brain tumours live longer and healthier lives.

S. John Liu, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Diffuse midline glioma is a deadly brain tumor that affects children. Radiation is the main treatment, since surgery and chemotherapy do not work well. New drugs are being tested, but they are not proven yet. To find better options, we built a new method that combines gene disruption with detailed study of brain tumors. This lets us test the role of many genes in new ways. We found genes that may help tumors respond better to treatment. Now, we will study how these genes work. Our goal is to discover new treatment combinations that can help children with glioma live longer and healthier lives.

Lillian Guenther, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

My group investigates specific features of pediatric bone tumors that allow them to survive. One cancer we are interested in is Ewing sarcoma. Ewing sarcoma is a common bone tumor in children. It is challenging to treat, particularly when the cancer has spread. We have become interested in a protein that is important for Ewing sarcoma cells. We want to understand what this protein does in cells. This will help us to kill Ewing sarcoma cells. We are also working with chemists to make new drugs to disrupt its activity. We will test these in Ewing sarcoma cells. Our hope is that these studies will eventually lead to new treatments for Ewing sarcoma.

Markus Müschen, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Many children survive with current treatments but when the disease recurs, it is often deadly and as such we need new treatment options for these children.In most cancers, a protein called beta-catenin is highly prevalent, making cancer cells grow faster. We thought this would be true for ALL but found the opposite. In ALL, beta-catenin is kept at very low levels because the cells quickly break it down. When it does appear, it works with a partner called LEF1 instead of its usual partner, TCF7. This pair slows cancer growth and can even make the cells die.This means ALL cells are very sensitive to beta-catenin buildup. We can use this weakness to our advantage. We have found four kinds of existing drugs, already tested in people for other diseases, which block the breakdown of beta-catenin in different ways.Our goal is to test these drugs to see which works best against ALL that does not respond to chemotherapy. Because these drugs are already known to be safe, we can move faster toward clinical testing in children. If successful, this approach could give new hope to families facing relapsed leukemia.

Evan Weber, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Pediatric cancer patients have greatly benefited from CAR-T cell therapy, which is a treatment that uses a child’s own T cells – a type of immune cell – to find and kill cancer. This approach has helped many children with blood cancers, but fewer than half stay cancer-free after one year. One reason for this is that sometimes CAR-T cells don’t survive long enough in the body to stop the cancer from returning. To fix this issue, we are trying to develop ways to make CAR-T cells act more like marathon runners that stay in the fight instead of sprinters that slow down too soon.My research focuses on the bone marrow, which is the part of the body where some blood cancers hide and where CAR-T cells go to fight them. We’ve found that the bone marrow sends out special signals that affect how well CAR-T cells survive. In this project, we will study those signals and use what we learn to create longer-lasting CAR-T cells. This work could ultimately make CAR-T therapies work better for kids and adults and inform other approaches to help these powerful immune cells stay active longer.