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Type: Game-Changerdfdhd

David Potter, MD, PhD

Funded by the Foligno Face-Off in honor of Janis Foligno in partnership with Hockey Fights Cancer powered by the V Foundation

The Game-Changer Challenge: Identify what drives hormone therapy resistance in breast cancer and stop it.  We have discovered a way by which fats found in some processed foods and cooking oils promote breast cancer.  This occurs in 40% of breast cancer and happens when oils undergo conversion to harmful fats that promote breast cancer.  These patients have a mutation in a gene called PIK3CA.  When this problem occurs, breast cancer doesn’t respond to hormonal treatment.  We have found a way to solve this problem in breast cancer by using a new drug developed from the diabetes drug metformin to block production of these harmful fats.  In collaboration with Dr. Matthew Goetz (Mayo Clinic) and our group (Masonic Cancer Center, University of Minnesota) we have found a way to use this new drug to improve treatment.  We can now restore sensitivity of breast cancer to treatment by adding our new drug to standard therapy in a mouse model.  In the proposed studies we plan to develop a combination of our new drug and standard of care drugs to get better results for patients. We have also discovered how the harmful fats promote breast cancer.  Using our animal model we also seek to identify ways to further block this harmful fat pathway causing breast cancer progression.  Our long-term goal is to test this new drug in a clinical trial in advanced breast cancer. Our goal is to benefit patients whose breast cancer failed to respond to treatment because of these harmful fats.

Peter Hosein, MD

Funded in partnership with the Dolphins Cancer Challenge (DCC)

Pancreatic cancer is one of the deadliest cancers, and most patients are not helped by immunotherapy. Immunotherapy is a treatment that uses the body’s own immune system to fight cancer.Our team is working with a cancer vaccine called ELI-002. It trains the immune system to find and attack pancreatic cancer cells. These cells carry a gene change called KRAS. In an earlier study, three of our patients had their cancer come back after the vaccine. They then took a different drug called nivolumab, and their tumors disappeared. This was a big surprise, because pancreatic cancer almost never responds this well to immune therapy.We think the vaccine trained the immune system well. But something in the tumor was still blocking the immune cells from finishing the job. New data from these patients’ tumors gives us a clue. A drug called daraxonrasib blocks the KRAS gene itself. This drug may clear the block and help the immune system work even better.This project will study tumor samples and use mouse models to learn how this combination works. Then we will test the vaccine together with the KRAS-blocking drug in a clinical trial. Some patients will also get nivolumab. Our goal is to find a better treatment for pancreatic cancer patients and learn which patients are most likely to benefit. This way, we can help many more people than the three patients whose amazing results inspired this research.

Thomas Alexander, MD, MPH

Funded in partnership with the Carolina Hurricanes, Hockey Fights Cancer and the Pediatric Cancer Research Foundation – Dribble for Victory Over Cancer

Children with brain tumors and other solid cancers often need genetic testing before doctors can confirm the diagnosis and choose the best treatment. Today, this usually means several different tests. Many hospitals also have to send tumor samples to another laboratory. Families may wait weeks for results. During that time, treatment can be delayed, and the wait adds stress.Our goal is to replace this process with one test that gives the same answers in about three days. The test uses a new method to study the tumor’s DNA. It looks for changes in DNA that drive cancer. Our team has already shown that this method can find important DNA changes in childhood leukemia. We have also seen promising results in brain tumors and other solid cancers. In this project, we will improve the test, show that it works well in a hospital laboratory, and study how it performs in everyday patient care.We will learn if this test gives answers faster and helps doctors choose treatment sooner. Our goal is to make this testing available within days instead of weeks. Faster results could help children start the right treatment sooner. If successful, this approach could improve care for children with cancer and help more hospitals offer precision medicine.

Geoffrey Uy, MD

Funded by Kelly Chase and the St. Louis Blues Alumni 2025 Puck Cancer charity hockey game in support of Hockey Fights Cancer powered by the V Foundation

AML (acute myeloid leukemia) and MDS (myelodysplastic syndrome) are serious blood cancers. In some patients, these cancers have a genetic change that makes them much harder to treat, and most current treatments do not work for very long. Our research is testing a new way to turn this weakness against the cancer. Cancer cells are like cars driving with damaged brakes. They keep growing even when their DNA is damaged. We plan to combine an existing leukemia treatment with a new pill that blocks one of the cancer cell’s backup repair systems. One drug is decitabine, which is already used to treat AML and MDS. The other is a new pill that may stop cancer cells from fixing damage. We will conduct a clinical trial to test this new treatment combination. First, we will find a safe dose for giving the two drugs together. We will also look for early signs that the drug combination works better than either drug alone. Finally, we will study blood and bone marrow samples to understand how the treatment affects the cancer cells.

Paula Pohlmann, MD, MSc, PhD

Funded by the Cancer Vaccine Coalition (CVC)

The INTERCEPT‑HER2 study is testing a new vaccine for people with HER2‑positive breast cancer who have finished all standard treatments but still show tiny signs of cancer in their blood. These signs are called minimal residual disease (MRD). MRD cannot be seen on scans, but it can warn us that the cancer may return. Finding MRD gives doctors a chance to act earlier, when the cancer is very small and the immune system is still strong.The vaccine uses cancer proteins to train the immune system to find and attack cancer cells. Earlier studies showed that the vaccine is safe and can activate the immune system, so it may help stop the cancer from growing again. In this study, 45 patients who test positive for MRD in the blood will receive three monthly vaccine doses and then two booster shots. They will also have regular blood tests for up to three years to see if the cancer signals in their blood go down or disappear.The main goals are to learn whether the vaccine can delay or prevent the cancer from coming back and whether it can clear MRD from the blood. The study will also show how often people with breast cancer still have MRD after treatment. Blood samples will help researchers understand how the immune system responds to the vaccine. What we learn may guide a larger future study and could lead to new ways to stop breast cancer earlier, before it becomes harder to treat.

Sidharth Puram, MD, PhD

Funded by the St. Louis Blues in support of Hockey Fights Cancer powered by the V Foundation

Tumors of the throat (called oropharynx carcinoma or OPC) are on the rise in the US and worldwide. Most of these are caused by a virus, called human papilloma virus (HPV). Current treatment of these tumors is fairly effective. As a result, researchers have been trying to reduce treatment to avoid side effects and problems with speech, swallow, and taste. But a portion of OPC patients do not have good outcomes. We are interested in identifying these patients before treatment begins so we can give them the right treatments. We found that some cancer cells turn off virus expression and this makes them treatment resistance and causes poor survival. In this study, we will use human models of OPC to understand what turns HPV expression on and off. We will also learn how different cancer cells with or without HPV talk with other cells in the tumor environment such as fibroblasts and immune cells.

Maria Figueroa, MD

Funded in partnership with the Dolphins Cancer Challenge (DCC)

Chronic myelomonocytic leukemia (CMML) is a form of cancer of the blood in which malignant cells multiply very fast and accumulate, leaving no room for healthy cells to grow. This rare form of cancer does not respond well to current available treatments, leaving the majority of patients with very few options to find a cure. Even for patients who do respond to the treatments, the disease quickly comes back so that, overall, less than 20% of patients survive more than 5 years after the disease is first found. In our recent work, we studied a large group of CMML patients and analyzed their disease. We found that patients who did not respond to treatment all shared the presence of a gene known as PRAME, yet patients who did better never had this gene present. Very little is known about PRAME’s role in cancer cells in general and CMML in particular. Recently, new treatments have been developed that specifically kill cells with PRAME. While these new treatments are being studied in other cancers, their impact on CMML is unknown. Therefore, we will test whether these new approaches may be used for patients with this aggressive form of leukemia.

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.

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.