The All-Star Grant is a re-investment in previous V Scholar or Translational grant recipients who are invited to apply for a $1,000,000 grant payable over 5 years. Any type of cancer research is permitted. This grant also includes salary support for a mentored post-doctoral fellow, which supports the next generation of cancer researchers.
Funded by the Dick Vitale Pediatric Cancer Research Fund
What is the problem? Fusion-positive rhabdomyosarcoma is a rare and deadly childhood cancer of muscle tissue. It is caused by a rearranged fusion gene (PAX3-FOXO1) that acts like an “on switch” stuck in the “on” position. Only 39% of children with this cancer are alive five years after diagnosis. Today there is no targeted drug that attacks the root cause of the disease.What is “enhancer addiction”? The rearranged gene does not work alone. It hijacks two helper proteins, called CBP and p300, which chemically tag regions of DNA to keep cancer genes turned on. These tags build up at the cancer’s “enhancer” switches, and the cancer cells become addicted to them. Take away the tags and the cancer loses power.What will this project do? Our lab invented a new medicine called IHK-44 that blocks CBP and p300 from turning on enhancer (gene “on” switches). Over five years, we will (1) show exactly how the medicine stops enhancer addiction, (2) develop a tumor test that predicts which children will benefit most, and (3) make IHK-44 safer and more potent by tuning its chemistry. Then we will test it in mouse models of this cancer. Why does this matter? If IHK-44 works, it will become the first precision medicine designed specifically for fusion-positive rhabdomyosarcoma. This project is the critical step that moves a new drug from the laboratory toward clinical trials, giving children with this cancer a real chance at a longer, healthier life.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Our overarching goal is to develop new therapies for T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is a particularly aggressive pediatric blood cancer. In the past, researchers tried to target T-ALL with immunotherapies known as CAR T-cells, or CARTs. However, these approaches were usually unsuccessful. This is because surface markers used to label cancer cells are also found on CAR T cells themselves. This causes CARTs to commit “fratricide”. Thus, there is an urgent need to find targets that are unique to cancerous T-cells. Our research has identified one such target called P2RX5. P2RX5 is often thought to be inactive in humans because of widespread inherited mutations. However, we determined that the active version of this gene is still common in people of African and, to a lesser extent, Hispanic origins. What makes it particularly attractive is that CARTs don’t make P2RX5, but high-risk T-ALL cells do. Encouraged by these findings, we created an antibody that can latch onto P2RX5-making cells. We then converted this antibody into CARTs, dubbing them “CART-X5”. Early results showed that CART-X5s can kill cancer cells without harming themselves. Our current plan is to test this approach in mice with leukemia. We see this work as a first step towards clinical trials in humans. While CART-X5 could work only in patients of certain ancestries, the very same patients have far less access to immunotherapy. Bringing CART-X5 to the clinic would reduce these disparities.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Some children with liver cancer do well with treatment, but others have tumors that are hard to cure or come back. Our project focuses on hepatoblastoma, the most common liver cancer in children. We study a growth signal called Hippo-YAP. In normal cells, this signal helps control growth and repair. In some cancers, it can get stuck “on.” This may help cancer cells grow and may also push them into a more aggressive, stem-like state.We want to find the weak points that YAP-driven liver tumors need to grow. We will study this in mice and in small tumor models, called organoids, grown in the lab from patient samples. These models let us test many genes and then focus on the ones that matter most. We will also test new drugs that block TEAD, a protein that works with YAP, to see whether they slow tumor growth or make the cancer cells less aggressive.This matters because children with high-risk hepatoblastoma need better and safer options. Today, treatment often depends on surgery and strong chemotherapy, which can have serious side effects. By learning what these tumors depend on, we hope to identify more precise treatments. Over time, this work could help guide new therapies for children with liver cancer and may also help children with other cancers driven by the same growth signal.
Drs. Carbone and Yang at the University of Hawaii Cancer Center discovered a new inherited disease called BAP1 Cancer Syndrome. People with this condition are born with changes in the BAP1 gene, which puts them at higher risk for several cancers, especially mesothelioma—a deadly cancer of the chest and stomach lining often linked to asbestos. Whole families can be affected because the gene changes are passed down. Here’s the surprising part: even though BAP1 mutations cause cancer, the tumors in these patients often can’t spread easily. This means the cancer is less aggressive, and many patients live for years. Some have even been cured. Now, with support from the V-Foundation All-Star Award, Drs. Carbone and Yang are studying how these patients’ bodies fight cancer. Their goal is to use this discovery to help all cancer patients resist cancer spread, improve survival, and save lives. This research shows that understanding one family’s rare gene mutation could lead to big breakthroughs in cancer treatment for everyone.
Funded by the Stuart Scott Memorial Cancer Research Fund
As we continue this study of a new treatment called TriPRIL CAR-T cells for patients with multiple myeloma that has come back or not responded to treatment, we want to understand why the treatment works for some people but not for others.To do this, we will study samples of blood and bone marrow from patients over time. We will compare what we find to results from patients who received other approved CAR-T cell treatments.We will look at how the CAR-T cells behave and work, how the cancer and the bone marrow environment change, and whether the body develops a response against the treatment itself. We will compare patients who improved with the treatment to those who did not.In the end, what we learn will help us improve CAR-T cell treatments for multiple myeloma.
Blood cancers are challenging to treat. The main reason is that cancer is found at late stages, where current treatments often fail. To save more lives, we must change our approach. We need to shift our focus from treating late-stage disease to stopping it early. We can achieve this by understanding how cancer starts. Many studies report that warning signs appear decades before cancer diagnosis. As people age, mutated blood cells can form in the body. This raises the risk of blood cancer by twelve times. Our research found that more chronic inflammation within bones creates a hostile environment. This inflammation acts like fuel for mutated cells. It helps them grow while harming healthy ones. A primary driver of inflammation is obesity, a condition that affects 40% of U.S. adults, and is a cancer risk factor. This long lead time offers a vital window of opportunity for early treatment. We propose a strategy to starve these bad cells. We aim to cut off the fuel supply linked to cancer cells to prevent cancer. We will test how obesity-driven inflammation helps mutated cells grow and weakens the immune system. Using human and mouse models, we will determine whether anti-obesity treatments can prevent cancer. We will test whether these treatments can reduce cancer growth and improve immune function. We will use computational tools to find high-risk patients. This project will help detect and halt leukemia in people most affected by obesity. The goal is to prevent devastating diseases before they begin.
Our immune system has special cells called T cells that can recognize and attack cancer. Even though these tumor-fighting cells are often present, many tumors still grow because T cells stop working properly during cancer development. Cancers can be grouped into two main types based on how the immune system responds. Some are called “hot” tumors. In these cancers, T cells are able to enter the tumor, but the tumor environment weakens them so they cannot kill cancer cells. Other cancers are called “cold” tumors which comprise approximately half of all human cancers. In cold tumors, T cells are mostly missing from the tumors. Cold cancers do not respond well to immune-based treatments. Scientists still do not fully understand why T cells fail to enter cold tumors or why these cancers resist treatment. To study this, we created preclinical mouse models in which tumors grow naturally and show cold immune phenotypes. Using these models, we found that tumor-fighting T cells are present in nearby lymph nodes but do not move into the tumor. Over time, these T cells become resistant to immune treatments, which is linked to the loss of important genes needed for T cell function. In this project, we will study in mice and patients with cancer why T cells get stuck, fail to enter tumors, and stop responding to treatment. This research may lead to new ways to make immunotherapy work for patients with immune-cold cancers.
A brain cancer called glioblastoma is one of the deadliest cancers. Even with surgery, radiation, and chemotherapy, most patients only live about 15 months. The biggest problem is that the cancer almost always comes back. Scientists are still learning why this happens. Some cancer cells, called “persister cells,” can survive radiation therapy by going into a kind of hibernation. When treatment stops, these cells wake up and start growing again, causing the tumor to return. Think of it like weeds in a garden. If you don’t remove all the roots, the weeds grow back.Our research discovered that a protein called BRD2 helps these persister cells survive radiation. When we remove BRD2 from cancer cells in the lab, they die from radiation. But when we use drugs to block BRD2, some cells still survive. They find other ways to stay alive.We’re now testing drug combinations. These drugs block both BRD2 and the backup routes cells use to survive, stopping cancer cells from returning after radiation. Another problem is getting drugs into the brain. The brain has a natural wall that blocks most medicines. We’re creating tiny particles that can carry drugs past this wall. Think of them as special delivery trucks that know a secret path into the brain. If this works, we could have new treatments that stop brain tumors from returning after radiation. This would give patients more time with their families, changing this deadly cancer into a disease we can control.
Pancreatic cancer remains one of the most difficult cancers to treat. There is a clear need for more effective therapies. CAR-T cell therapy has shown promise in some cancers. However, pancreatic tumors create a harsh environment that weakens T cells and limits how they work. This project aims to reprogram T cells so they can persist and continue fighting in these conditions.T cells can be genetically engineered. This allows us to adjust the instructions that control how they behave. Most current approaches focus on removing barriers, like taking the brakes off. In this project, we take a different approach. We aim to strengthen T cells so they can better adapt and function within tumors.Our goal is to identify changes that make T cells more potent and longer-lasting. These insights will enable more effective CAR-T therapies for pancreatic cancer and other solid tumors.
Myelodysplastic syndromes (MDS) are a group of blood cancers that cause low blood cell counts. The most common problem is anemia, which means the body does not have enough red blood cells. This can make people feel very tired and often leads to the need for blood transfusions.In MDS, the bone marrow (where blood cells are made) shows higher levels of inflammation. The cells in the bone marrow produce proteins that increase this inflammation in the body. In this project, we aim to reduce inflammation by targeting a key system called the inflammasome. The inflammasome is a group of proteins that helps to produce a substance called IL-1beta, which can make the disease worse.We are studying a new drug called HT-6184 in our lab. This drug helps block the inflammasome and reduce inflammation. In early lab tests, it has lowered inflammation and increased red blood cell levels.In this study, we will first identify the proteins and cells that cause increased inflammation in MDS. Then, we will test ways to block these targets using antibodies and specific drugs in lab-grown cells and patient blood samples. Most importantly, we will test how well the inflammasome-blocking drug works in MDS blood samples and in mouse models of the disease. This drug has already been approved by the FDA for clinical trials.If our results are successful, this research could help move this drug quickly into clinical trials designed for patients with MDS.
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