Funded by the Dick Vitale Pediatric Cancer Research Fund
Immune checkpoint inhibitor therapy (ICT) is a form of cancer therapy that boosts the immune system to kill cancer cells. ICT can help cure some adult cancers but has not been effective in children with cancer. This proposal explores whether a combination of standard cancer therapy and ICT is both safe and effective in children with solid tumors in a clinical trial. First, we will test tumor, blood, and stool samples collected from patients in this clinical trial. We will attempt to learn what factors determine whether a patient will respond to this combination therapy or not respond. Second, we will use mouse cancer models to test different combinations of standard cancer therapy and ICT to see which combinations work the best. This work will help us understand if combining standard cancer treatments with ICT is both safe and effective in children with solid tumors.
Funded by the Stuart Scott Memorial Cancer Research Fund
Our research looks at how hormone receptors play a role in cancer. These receptors are involved in prostate, breast, uterine, and ovarian cancers. Normally, they help control important functions in the body. But as people get older and hormone levels drop, these receptors can stop working properly and help cancer grow.
Even though there are treatments that block these receptors, many patients still see their advanced cancers return within two years. This happens because cancer cells find new ways to turn the receptors back on, which makes the treatments less effective.
To tackle this problem, we use advanced imaging tools, including high powered microscopes, to make 3D models of the hormone receptors. This helps us see how the receptors work and what goes wrong in cancer. We have already found new interactions at the molecular level that were not known before. With support from the V Foundation, we hope to create better drugs that target these receptors more effectively, helping to stop cancer from coming back and improve patient outcomes.
Cancer must change its nutrient uptake to grow. Drugs blocking cancer’s use of nutrients have been the basis of cancer therapy. However, most of these drugs work by blocking the pathways that metabolites use. They exhibit significant toxicity since they also harm normal tissues. We are looking at metabolite-targeted therapies that are less toxic. We hope the therapy will be more specific and effective as well. We don’t seek to block metabolite pathways. Instead, we target the specific metabolites that change in the tumor microenvironment. We study and harness the power of our body’s metabolites as drugs. Our work has the potential to change how we target cancer, leading to less toxic and more effective drugs. Our work will also help to diagnose cancer.
Funded by the Dick Vitale Pediatric Cancer Research Fund
The most common cancer in children, including teenagers, is a blood cancer named leukemia. Chemotherapy is the main treatment for pediatric leukemias. Although most patients respond well, some do not, leading to poor outcomes. Chemotherapy can also have negative side effects both during treatment and for the rest of their lives.
Patients who don’t get better with chemotherapy are those that have one of most common genetic changes, the rearrangement of a gene called KMT2A (KMT2A-r). In a study at The University of Texas MD Anderson Cancer Center, patients with KMT2A-r leukemia survived for 6 months after 2 chemotherapy treatments and only 2.4 months after 3 or more treatments. Scientists are looking at new ways to treat these patients and help them live longer.
Menin inhibitors could be a good option because they target KMT2A-r leukemia and have fewer side effects than chemotherapy. But some patients with KMT2A-r leukemia can also have mutations in other proteins that don’t let the menin inhibitors work as well by themselves.
With the help of the V Foundation, Drs. Andreeff, Carter and, Cuglievan, at MD Anderson Cancer Center plan to test different combination treatments that target menin and other proteins at the same time to get better results. This can potentially help children with KMT2A-r leukemia live longer and have better lives.
Funded with support from the Scott Hamilton CARES Foundation
A new kind of treatment for cancer that helps people’s bodies fight off the disease has allowed some patients to live longer, healthier lives. These new treatments, however, do not work for every type of cancer or for every patient. Solid cancers, in particular, are very good at protecting themselves from these therapies. Also, these new drugs are very difficult and expensive to make and sometimes can cause dangerous side effects.
The overall goal of this proposal is to make a safer and cheaper, but just as powerful, new treatment for solid cancers. For more than ten years, I have worked to develop better, safer cancer therapies. One of these new drugs was just tested in cancer patients and some people responded really well. When patients get this therapy, it acts like a delivery truck, dropping off special instructions to the body and teaching it how to cure cancer all on its own. Because not everyone who received the therapy responded to it, we are writing better instructions so that more patients will have better results. In this proposal, we hope to test these new and improved instructions in mice and see if they can cure cancer. Overall, if this work is successful, we will have discovered a new approach to treating cancers that we can then test in humans.
One challenge of lung cancer treatment is that cancer cells thrive in a tumor ecosystem (or habitat) that protects them. This tumor ecosystem consists of immune cells, blood cells, connective tissue that allow lung tumors to grow and spread to organs (brain, bones, liver, lungs). We recently discovered that PD1, AXL and STAT3 signals in lung cancer serves as “on switches” that drive lung cancer growth, treatment resistance and spread to organs. More importantly, these cancer signals allow cancer cells to communicate with nearby cells for protection. We found that blocking PD1, AXL and JAK signaling can block communication between tumor and non‐cancer cells in tumorecosystem. Our research team would like to perform mouse experiments and clinical trial using drug combinations that turn off these signals and disable the tumor within its habitat, thereby preventing tumor growth and spread. This therapy could help improve survival for our patients with lung cancer.
Surgery is the main treatment option for patients with rectal cancer. During surgery, the surgeon’s main goal is to completely remove cancer tissue without leaving cancer behind. However, not all diseased tissue can be seen with the surgeon’s eye, especially after radiation when tumor and scar look similar. Because of that, it is hard for a surgeon to be certain that all cancer tissue has been removed on the anal side to help preserve the anus and avoid a permanent bag. The same problem happens for adjacent organs such as the pelvic nerves, pelvic sidewall, vagina or prostate that may appear to be affected. Consequently, 4-20% of patients have recurrence while 20-50% have postoperative complications. Currently, there are no technologies that can help surgeons identify cancer tissues within the rectum and nearby organs in vivo during surgery. Surgeons are thus faced with the difficult decision to excise questionable tissue that could be affected by cancer at the devastating expense of compromising critical tissue structures and quality of life. In our study, we will evaluate the MasSpec (MS) Pen technology for tissue identification in rectal cancer surgery. The MSPen provides the transformative capability of detecting molecules diagnostic of cancer in tissues in vivo, without tissue damage. We will refine the MSPen for rectal surgery and evaluate its performance in identifying rectal cancer and normal tissues. The MSPen has the potential to help surgeons achieve complete cancer removal and preserve normal tissues, thus improving treatment, outcomes, and quality-of-life for patients.
Funded by Kay Yow Cancer Fund 2023 Final Four Research Award
One of the greatest challenges in cancer treatment is that response to standard treatment is frequently incomplete and causes many side effects. Current treatments are often ineffective because they function as a “one-size-fits-all” approach to a very personal disease. This lack of success is magnified in triple negative breast cancer (TNBC), which differs greatly between each individual. We have recently discovered a protein that is not expressed anywhere in females, except in TNBC tumors, where it is required for tumor growth. This protein is normally only found in male testes. Thus, this protein is a perfect target to inhibit tumor growth without impacting normal tissues. Here we will study the function of ZNF165 and determine how it promotes growth of tumors. Ultimately, this work could lead to a tailored approach for treating TNBC without harming the patient.
New cancer drugs are needed to improve quality of care, deliver cures, extend life and prevent relapse. We need to hunt in new places or in places that are not yet fully explored to come up with ideas for better drugs. We have focused on a previously overlooked area that is prime for exploitation, namely how DNA is packaged into cancer cells. DNA is the instruction manual of the cell and must be copied forward when cancer cells divide, a process called DNA replication. However, because DNA is so long it must be packaged correctly into the cell nucleus after it is copied. The cell makes a large number of DNA-packing proteins called histones to accomplish this task. We aim to find ways to attack a cancer cell’s ability to make histone proteins as a new cancer treatment strategy. We expect this be safer (less toxic) than targeting DNA replication itself, and hope to find ways to target it specifically to cancer cells. To do this, we are focused on the details of the DNA packing problem, by digging into the cellular components that control this process and asking molecular questions using the latest technologies. We want to understand how this process works better and how it goes awry in cancer cells so that we can exploit our findings for new drugs.
Liver cancer is among the top four causes of cancer death. Historically, liver cancer is driven by HCV. Now, liver cancer is the fastest-growing cause of cancer death in the United States. This is due to the increase of nonalcoholic fatty liver disease (NAFLD), affecting around 25% of the global population. Emerging evidence defines over-nutrition environment and circadian misalignment as risk factors for NAFLD and liver cancer. So far, there is no FDA-approved drug to target the progression of NAFLD to liver cancer. Therapeutic approaches for liver cancer are also limited. Therefore, it is important to understand the mechanisms behind NAFLD-related liver cancer and identify new therapeutic targets.
We reported that a lipid-lowering drug decreased liver fat more when given in the afternoon than when given in the morning. This work is an example of chrono-pharmacology, where giving drugs at specific times of the day can maximize efficacy. My recent work revealed eating time as a key pacemaker for rhythmic metabolic processes in the liver. We can find a potential preventive approach for metabolic disorders and cancer patients by exploring this relationship between the internal clock and eating time. Chrono-nutrition is adjusting diet schedules to maximize results for treatment. The future project will identify how circadian rhythm affects liver cancer cells. These studies aim to find new targets of circadian physiology and reveal insights into liver cancer prevention and treatment.
