Florida Archives - V Foundation

Jashodeep Datta, MD

Pancreatic cancer is very hard to treat. Even after surgery, it often comes back. One reason is the tissue around the tumor. This tissue can help the tumor grow and hide from treatment. Our work targets a key set of harmful signals in this tissue. Many of these signals use one helper protein, called IL1RAP. We will test a drug called nadunolimab that blocks IL1RAP. We hope this will quiet these signals and help standard treatment work better, especially when treatment is given before surgery. We will study the effect of IL1RAP in two main cell groups: 1. certain white blood cells that can block the body’s immune attack, and 2. support cells that can build a barrier around the tumor. We will also study tumor samples from patients. We will test whether the presence of IL1RAP-rich cell “neighborhoods” predict how well treatment works or does not work. In animal models of pancreatic cancer, we will test if adding nadunolimab before surgery can delay or prevent relapse after surgery. Finally, we will develop simple tissue and blood tests to show early if the drug is working. These tests can guide future trials and improve care for people with pancreatic cancer.

Elsa Flores, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund

Cancer happens when certain genes change and cells grow out of control. New efforts look closely at each patient’s tumor so researchers and doctors can pick treatments that shrink that tumor. This is important for finding ways to treat pathways that are hard to target with drugs. One of the hardest to fix is TP53 (also called p53), the gene most often changed in cancer. Because p53 helps normal cells work, trying to target it directly can cause harmful side effects. To get around that, our research studies two related genes, TP63 and TP73, which can do some of the same jobs as p53 to stop tumors from growing. Our earlier V Foundation funding in 2005 helped us discover new roles for TP63 and TP73, and now we plan to use the pathways they control to make up for lost p53 function. This idea may work better than trying to fix p53 directly, since those methods are often only partly effective or only work for certain mutations. We also found special non-coding RNAs that affect how tumors grow and respond to treatment. The new therapies we propose aim to target tumors precisely and cause less harm to patients. Although we focus on lung, breast, and ovarian cancers, these approaches could help any cancer with TP53 mutations.

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.

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.

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.

Brian Czerniecki, MD, PhD

Funded by Hooters

Breast cancer is the most common cancer type and 2nd leading cause of death by cancer for women in the US. Patients with early-stage breast cancer or DCIS can survive. But there are groups at high risk for the cancer coming back or developing invasive breast cancer (IBC). These patients are treated with surgey, radiation, and other types of therapies. While these treatments often work, recurrence and IBC are still problems. Our project aims to create a therapy using the patients’ immune system. This therapy will help the body to recognize and engage in the fight against their cancer. If successful, this therapy will be the first non-estrogen inhibitory immunotherapy. And this therapy will help prevent the cancer from coming back and prevent IBC.

Christina Von Roemeling, PhD

Funded with support from Hockey Fights Cancer in honor of Ben Stelter

Glioblastoma (GBM) is the deadliest adult brain cancer. Even with standard of care treatment, survival rates are low. A major challenge is that the brain’s protective barrier blocks most drugs. The tumor also weakens the immune system, making it harder for treatments to work. CAR-T cell therapy is a promising treatment that trains T cells, a special immune cell, to recognize and attack cancer cells. It works well in other cancers, but not GBM. Normally, T cells follow signals from proteins called chemokines and cytokines to locate and fight disease. However, GBM blocks these signals, stopping T cells from working properly. Our study will develop a new immune gene therapy using a harmless virus called AAV to help the immune system fight GBM. This therapy reprograms nearby brain cells (called astrocytes) to send signals that attract and activate immune cells, including CAR-T cells. Our gene therapy will deliver two key proteins: CXCL9 (which attracts T cells) and IL-2 (which helps them grow and stay active). This targeted approach ensures a steady immune response right at the tumor. We will combine this immune gene therapy with CAR-T cells to improve their ability to find, survive, and attack the tumor. Our research will study how AAV works in the brain, activates CAR-T cells, and which AAVs can be used in human clinical trials.

Erin George, MD

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.

Defne Bayik, PhD

Funded in partnership with the Dolphins Cancer Challenge (DCC)

Glioblastoma (GBM) is the most frequent and deadly malignant brain tumor. Escape from the body’s immune response is a critical factor that makes GBM untreatable. One promising anti-GBM strategy is to augment the tumor-fighting capacity of immune cells. CD8+ T cells have the potential to kill tumors, but cancers make them not function properly. Strategies that aim to prevent this process have not been successful in GBM yet. We recently found that a molecule named dipeptidyl peptidase 4 (DPP-4) is present on dysfunctional T cells at high levels. Furthermore, we observed that DPP-4 prevents CD8+ T cells from killing tumors. In this application, we aim to determine how DPP-4 reprograms T cells to a nonfunctional state. DPP-4 inhibitors are commonly used by patients with diabetes. We seek to repurpose these drugs in combination with existing immune-activating strategies to improve T cell response against GBM. Collectively, these studies will define DPP-4 as a new treatment target in GBM.

Jay Spiegel, MD, FRCPC

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.