Funded by the 2025 Kay Yow Cancer Fund Final Four Research Award
Ovarian cancer is hard to treat. Most patient’s cancer comes back after standard treatment. Once the disease is back it is more difficult to treat and patients will eventually die from it. Chemotherapy can also cause direct harm to the body. This can make patients delay treatment, stop it altogether, or lower their doses. It can also harm the good bacteria in the gut, which is important for how well treatments work. Our goal is to come up with new ways to predict, prevent, and manage these harmful effects. We also want to develop new therapies that can lead to complete and lasting responses, increasing chances of cure right from the start. To reach this goal we will use mathematical modeling. This will allow us to test many treatments quickly, which cannot be done with traditional laboratory methods. First, we will use patient blood samples to predict the risk of toxicity, helping doctors know when to change or pause treatment. Next, we will use math modeling to find the best combinations of new targeted therapies. Finally, we will reduce the harmful effects of chemotherapy on the gut using math modeling to improve how well those therapies work. This research could change how we treat cancer. It may lead to complete tumor response and better chances for a cure.
Funded by the V Foundation Wine Celebration in honor of Mike “Coach K” and Mickie Krzyzewski
Pancreatic cancer is the third leading cause of cancer death in the United States. Treatments have changed very little in recent years. One challenge is that there are different “subtypes” of pancreatic cancer, so tailored therapies are desperately needed. Our lab found that drugs that block a protein called cyclin-dependent kinase 7 (CDK7) can kill the basal subtype, which is the most lethal. It makes up a quarter of pancreatic tumors and has the worst overall survival. We propose to study a drug that blocks CDK7 in patients with early-stage pancreatic cancer, after chemotherapy and before surgery. This funding will allow us to work with Carrick Therapeutics, who is giving us a supply of drug for the clinical trial. Our ultimate goal is to offer a new targeted treatment option and hope to pancreatic cancer patients.
Funded by Kelly Chase and the St. Louis Blues Alumni Puck Cancer charity hockey game in support of Hockey Fights Cancer powered by the V Foundation
This proposal presents a plan to collect and manage blood samples from patients getting stem cell transplants. In this treatment, unhealthy blood-forming cells (stem cells) are replaced with healthy ones. With help from the V Foundation, this research will set up and manage a new system for storing these transplant samples at Washington University in St. Louis. The study will look at detailed biological data from 40 patients who receive these transplants. These patients will have different types of donors: siblings who match, unrelated donors who are matched and unmatched, and partially matched family members. The goal of the transplant sample storage program is to help researchers at Washington University find ways to make stem cell transplants safer and more effective for treating blood cancers.
This research will also help understand how new drugs that suppress the immune system work. With the support of the V Foundation, this project supports their mission to defeat cancer.
Funded by the St. Louis Blues in support of Hockey Fights Cancer powered by the V Foundation
Therapies that modulate the immune response avoid the harmful side effects of standard cancer therapies and also have the potential to be more effective and longer-lasting. The most successful immune therapies to date rely on engineering a specific type of immune cells, T cells, to target and kill cancer cells. These therapies can be curative for some, but unfortunately still do not achieve their potential of cure for most. Our lab has identified a specific molecular pathway responsible for controlling the function of these immune cells. The goals of this project are to first understand how the driver of this pathway, a protein called BACH2, regulates engineered T cell function. Second, we aim to use advanced protein engineering tools to control the activity of BACH2, allowing us to thereby control engineered T cell function at will. If successful, these studies will shed light on a previously under-appreciated pathway that lies at the center of T cell function. Further, they will layout a pathway for “remote control” of BACH2 and nearly any T cell molecular program, allowing precision control of this potent anti-cancer therapy.
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.
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.
Funded in partnership with WWE in honor of Connor’s Cure
Pediatric Diffuse Midline Gliomas (DMGs) and High-grade gliomas (HGGs) are aggressive brain tumors. Unfortunately, current treatments don’t work well for these tumors. Our research shows that energy pathways play a role in making these tumors resistant to treatment. Specifically, proteins involved in energy use become more active in resistant tumors. Our recent findings suggest that disrupting these pathways could be a new way to fight these tumors.
In our upcoming study, we will test a compound that acts like glucose but interferes with energy use. We will also test other ways to target the weaknesses of these tumors. Our tests will measure protein and gene activity, energy use, and how combination treatments work.
Funded in partnership with Miami Dolphins Foundation
Cancer immunotherapy has been one of the great advances in the treatment of cancer in the past decade. In B-cell cancers, hijacking T-cells by insbertion of a synthetic receptor (CAR-T cells) enables these cells to recognize and kill lymphoma through a specific marker (CD19). However, despite CAR-T leading to high rates of remission, only about 40% of patients are cured. Some major causes for why CAR-T does not work in patients is too great a burden of tumor cells and the cancer learning to hide the target the CAR-T needs to be effective. Therefore, there is great interest in combining CAR-T with other cancer therapies to improve efficacy. We have a clinical trial combining 2 drugs, mosunetuzumab and polatuzumab, targeting other lymphoma markers (CD20 and CD79b), together with CAR-T in patients with aggressive B-cell lymphomas. Using this approach, we hope to improve outcomes by addressing the main reasons for CAR-T failure. In this grant, we will track a patient’s response to treatment by monitoring a patient’s blood for small tumor fragments, to allow us to determine when extra therapy is needed in addition to CAR-T. We will precisely measure the amount of target markers on lymphoma cells to assess its importance for success of this therapy. Lastly, as CAR-T therapy has a high risk of infection, we will monitor recovery of the immune system to learn how adding extra therapies may affect a patient’s risk.
