Illinois Archives - V Foundation

Raymond Moellering, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Burkett’s lymphoma and neuroblastoma are two different types of childhood cancers that share a common link: the MYC gene. Chemotherapy is often used for treatment, but the side effects can be hard on young patients. Doctors and researchers now know that the side effects are mostly from blocking the growth of both cancer cells and healthy cells. Chemotherapy also does not work well for some patients. Our research focuses on drugs that target MYC to safely slow the growth of cancer cells. We will test these new drugs in the laboratory for future development into medications for patients. In the end, our work will produce better medicines to treat these cancers without giving up patient comfort.

Yuxuan Miao, PhD

More people are getting head and neck cancer caused by the human papillomavirus (HPV). Traditional treatments like surgery or radiation can cause strong side effects. Sometimes, the cancer comes back. Because of this, doctors are looking for safer and better ways to treat these cancers. Immunotherapy is a newer treatment. It helps the body’s immune system find and destroy cancer cells. Some people with head and neck cancer do well with a type of immunotherapy called “immune checkpoint inhibitors.” But, patients whose cancer is caused by HPV usually do not benefit as much. A new immunotherapy called HB-200 is being tested. It is designed to help the immune system better find and attack cancer linked to HPV. Early studies show that HB-200 may work for patients with HPV-positive cancer, even if other treatments have not helped. Our research looks at tumor samples from people with and without HPV. All of these patients received different types of immunotherapy. We are using simple lab tests and special tools to learn why HPV-related cancers do not respond well to older treatments, but do respond to HB-200. Our goal is to make HB-200 better and find new ways to treat these cancers. We hope this will lead to better care and longer, healthier lives for patients.

Martina Damo, PhD

Funded by the V Foundation Chicago Epicurean in honor of The Debbie Jones Family

Cancer immunotherapy with checkpoint receptor inhibitors (ICIs) causes autoimmune side effects. These side effects occur in most patients treated with ICIs. These side effects are debilitating and difficult to treat. My goal is to find treatments for ICI side effects. I developed new mouse models where ICIs induce the same autoimmune side effects as in humans. I will use these models to understand why ICIs are toxic. I will also understand how to treat the side effects of ICIs.

Brandon Faubert, PhD

Funded with support from Hockey Fights Cancer powered by the V Foundation presented by AstraZeneca

Lung cancer is a deadly disease. This lethality is due, at least in part, to how often and how extensively these cells can spread throughout the body. My laboratory is working to understand what causes these cancer cells to spread and how they survive this process. By doing so, we hope to identify new ways to treat lung cancer.

We are interested in the nutrients cancer cells use to support growth and how these nutrients might help cancer cells spread. We are particularly interested in fats, or fatty acids. These complex nutrients play many different roles in cells, including helping to maintain cell structure, storing energy, and even acting as a method of communication with other cells. When we measured fatty acids in lung cancer, we saw that several fats and fatty acid pathways were different in tumors that spread throughout the body, compared to tumors that did not. In this study, we investigate how fatty acid metabolism supports aggressive cancer cells, and we will test whether blocking these fatty acid pathways can prevent lung cancer cells from spreading.

Xiao-Nan Li, M.D., Ph.D.

Funded by the Dick Vitale Pediatric Cancer Research Fund and the StacheStrong Foundation

Clinical outcomes in children diagnosed with high grade glioma and diffuse intrinsic pontine glioma remain very poor. Even with surgical resection, chemotherapy and radiation, most of the tumors eventually relapse. This is primarily because some cancer cells develop resistant to the therapies that doctors prescribe. For the past 50 years, the identities of these therapy-resistant cancer cells remain unknown. Difficulties of obtaining relapsed tumor tissues and limited availability of animal models are the major reasons why we still don’t have new treatment. With the strong support of patients and families, we have developed a panel of animal models by directly implanting brain tumor cells into the brains of immunodeficient mice. We can now use these models to mimic what happens in children but treating the animals with the similar drugs/radiations. These models are very helpful. Indeed, our preliminary study in a small number of models have identified a set of cells expression CD57 as candidate root cells as they were found before drug treatment, remain present after very extensive clinical treatment, and can even survive the most harmful environment with no oxygen and no nutrient. This exciting finding has promoted us to perform a detailed analysis using more animal models to confirm the extraordinary capacity of the CD57+ cells in resisting therapy induced cell king, to understand how they can survive current treatment, and to find new drugs and strategies to selectively kill these seed cells. Our ultimate goal is to find new cure for children with highly malignant gliomas.

Alexander Muir, PhD

Funded by the V Foundation Chicago Epicurean in honor of Marc Silverman and in memory of Jeff Dickerson

Cells require nutrients to fuel their metabolism to sustain life. Healthy tissues are fed nutrients by blood vessels in a process called perfusion. In contrast, cancers have dysfunctional blood vessels. Compared to normal tissues, blood vessels dysfunction in tumors limits perfusion. This limited perfusion results in abnormal nutrient levels in tumors. We have found that abnormal nutrients in pancreatic tumors blocks the ability of chemotherapeutic drugs to kill pancreatic cancer cells. This is an important finding as pancreatic tumors are resistant to chemotherapeutics, which causes high mortality in this disease. We propose that: (1) identifying the nutrients in pancreatic tumors and (2) how these nutrients lead to chemotherapeutic resistance could lead to new treatments to improve patient chemotherapy outcomes. These are the two critical goals of the proposed project.

To identify the metabolic stresses in tumors that cause chemotherapeutic resistance, we searched for nutrients in tumors that cause chemotherapy resistance. We found that certain amino acids accumulate to high levels in tumors and cause chemotherapy resistance. We will determine if blocking tumor accumulation of these amino acids can improve the chemotherapeutic treatment of pancreatic tumors. Toward the second goal of identifying how amino acid accumulation causes therapy resistance, we will use advanced biochemical and genetic tools to determine how the amino acids accumulating in tumors enable pancreatic cancer cells to survive chemotherapy treatment. Completing aims will provide new insight into how nutrients in pancreatic tumors cause chemotherapy resistance and provide clinically actionable approaches to improve chemotherapy response in patients.

Lillian Eichner, PhD

Funded with support from The Orr Family Foundation

Lung cancer is the most common source of cancer-related death in the U.S. and worldwide. Lung cancer is a heterogeneous disease, with multiple subtypes characterized by different genetic and molecular profiles, and different response to treatment. One subset of lung cancer is caused by the loss of a gene called LKB1, and approximately 50,000 people are diagnosed with this type of lung cancer in the U.S. each year. Currently, no available therapies elicit sustained clinical benefit for patients with LKB1-mutant lung cancer, and the current overall survival time for such patients from the time of diagnosis is less than one year. Thus, there is great unmet need to rapidly discover and translate clinical options to help these patients. Our recent work has discovered a mechanism of therapeutic resistance (an explanation why tumors do not respond to therapy) that is specific to LKB1-mutant lung tumors. We discovered that two available, clinically-tolerated drugs together can overcome this mechanism, and we are working toward clinical translation of this finding. However, we predict that this finding is only the tip of the iceberg, and that we are poised to discover additional promising therapy approaches as well. Therefore, it is now imperative to fully characterize the mechanisms of therapeutic resistance in this tumor type, as we will do in this project, to expand our understanding of how to treat patients with this disease. The hope is that this study will pave the way toward improved therapeutic options for patients with lung cancer.

Megan McNerney, MD, PhD

Co-funded by the Dick Vitale Pediatric Cancer Research Fund and the Jeff Gordon Children’s Foundation

Children with cancer are typically treated with chemotherapy to kill all dividing cells, including tumor cells. This general treatment causes side-effects, including damaging the normal healthy cells children need to grow and thrive. An additional, devastating, long-term side-effect of the use of chemotherapy is the risk of developing a second cancer. To circumvent these toxicities, we propose a targeted treatment tailored for a subset of pediatric patients with blood cancer. We identified a gene called “CUX1” that is deleted in the blood cells of patients with certain types of leukemia. Loss of one copy of CUX1 causes blood cells to grow too fast and stop maturing. In the current proposal, we predict that a drug that increases CUX1 levels will prevent leukemia growth and restore normal blood cell maturation. The objectives of the current proposal are to identify druggable regulators of CUX1 and to use these compounds to restore CUX1 in leukemias with CUX1 loss. We have identified one candidate regulator, named GSK3. We hypothesize that inhibition of GSK3 will increase CUX1 levels, halt leukemia growth, and restore normal blood development. We will accomplish these studies using innovative genetic screening, novel mouse models of childhood leukemia, and patient leukemia samples. Accomplishing the proposed studies will aid in the development of non-toxic therapies for children. This work will help us achieve our long-term goal of devising urgently needed treatments to improve the outcome for high-risk leukemias of childhood.

Daniel Arango, Ph.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Liver cancer is a leading cause of cancer-related deaths. Its incidence continues to increase, posing a significant threat to public health. A leading risk factor is the chronic exposure to liver stress, which, in turn, enhances the uncontrolled division of cancer cells and tumor growth. Proteins are the functional units within cells. They are made from the instructions stored in DNA and carried by messenger RNA (mRNA) through a process known as translation. Notably, the information stored in DNA is not static and can be modified to alter the outcome of translation to promote cancer growth. Two of these modifications are called ‘RNA oxidation’ and ‘RNA acetylation’, which are induced in liver cells in response to cellular stress, and their levels correlate with tumor growth. Thus, this study will investigate how the interplay between RNA modifications and translation promotes liver cancer. The results obtained in this study will allow for future clinical efforts to fight liver cancer.

Colby Thaxton, MD, PhD

Funded by Constellation Gold Network Distributors

The cells in the human body are constantly subjected to stress, which is linked to changes in cellular metabolism. Our research team, and others, have made connections between these cell conditions and cancer. Our central question is: Can we make a simple blood test that provides an accurate measure of ongoing cell stress and metabolic changes to gauge an individual’s risk of cancer? This test may provide more than just a snapshot measure of cancer risk. For example, the test could be used to measure how lifestyle changes modify cancer risk across the lifespan. To answer our question, we developed expertise that enables rapid measurement of signals in certain blood cells attributed to changes in cell stress and metabolism. Our study will determine if these signals can be used to quantify cancer risk. We will obtain blood samples from individuals without cancer, from individuals who have a condition known to increase their risk of cancer, and from individuals diagnosed with cancer. We will isolate certain cells from these samples and then measure the candidate signals in the cells. We anticipate our studies to reveal that the signals we are measuring will be the lowest in healthy individuals, will increase in individuals with the precancer condition, and will be highest in people diagnosed with cancer. These findings would powerfully validate our technology and suggest that individuals may benefit from our test for the early detection, and even prevention, of cancer.