Funded by Lloyd Family Clinical Scholar Fund
New, non-chemotherapy treatments that use a patient’s own immune system have transformed the treatment of Hodgkin lymphoma (cHL). Typically used in patients with cHL that is resistant to standard treatment, these immune therapies can control the disease for months to years. However, in the long run, most patients will not be cured. Early research suggests that these powerful drugs are safe to use as part of the first or second treatment in patients with cHL and using them earlier could lead to more cures. However, we have not done the research to clarify when is the best time to use immune therapy in cHL and to determine which drugs are best to combine with immune therapy in order to cure more patients.
My research will answer important questions about the best way to use immune therapy for cHL: (1) How should we use immune therapy as part of the first treatment to cure the most patients and reduce the side effects of our standard treatments? (2) How should we use immune therapy as the second treatment in patients who are not cured by their first treatment? (3) Can we predict which patients will respond best to immune therapies to help us choose the patients most likely to benefit from these new treatments? And, in cHL patients who are resistant to immune therapy, can we reverse the resistance?
Pancreatic cancer is a deadly cancer. There are urgent needs to identify specific biomarkers in blood (proteins and metabolites) that are related to pancreatic cancer. The increased understanding of risk factors for pancreatic cancer can be useful to develop new strategy for predicting individual risk of developing this cancer. The proposed study using novel design and methods will help identify protein and metabolite biomarkers in blood causally associated with pancreatic cancer risk. Knowledge generated by this project will help us to better understand the etiology of pancreatic cancer and lay a solid foundation for future efforts of risk prediction of this deadly cancer. The identification of high-risk individuals can be useful for more specific, expensive, and/or invasive tests to identify disease at an early stage or for targeted prevention to reduce disease risk.
Colorectal cancer is the second leading cause of cancer related deaths worldwide. Alarmingly, recent studies show that its incidence is increasing in younger adults. Certain environmental factors, such as diet, can have an impact on colorectal cancer. Calorie dense, western diets can lead to energy imbalance and excessive weight gain, which is associated with higher risk of colorectal cancer. Since diet is a modifiable risk factor, it is important to understand precisely how diet composition and particular nutrients within the diet can affect colon tumor cells directly and indirectly. We plan to systematically examine how colon cancer cells become dependent on certain nutrients that are necessary for rapid tumor growth and progression. We will also test how relevant dietary nutrients, such as sugars and fats, change the function of support cells found within the tumor and influence tumor growth. Our hope is to identify vulnerabilities in colon cancer cells that we can enhance through nutrition and develop new treatments that will improve survival and quality of life for cancer patients.
The goal of this project is to make new drugs against ovarian cancer genes using a new drug discovery method. Ovarian cancer (OC) remains a deadly disease. OC will be diagnosed in over 21,000 women in the United States this year and 13,770 patients are expected to pass away during this time. While initial responses to the best anti-cancer drugs are frequent, most patients with OC will experience disease again after 24 months of treatment, and most women will unfortunately pass away from this disease within five years. Thus, there is an urgent need to make new drugs to treat ovarian cancer. The classic approach to drug discovery is both time intense and costly, and most cancer drug discovery is focused on making drugs against cancer proteins whose shape is considered readily ‘druggable’. Our central premise is that many ovarian cancer proteins can be drugged. To test our idea, we will use a new tool that finds druggable proteins by detecting drug binding to cancer causing proteins in OC cell lines and patient tumors. If successful, this program should develop a new class of anti-cancer drugs to help women suffering from OC.
Fighting cancer is like a game a chess: each treatment can be followed by the adaptation of the tumor. Our next move requires the development of a novel treatment strategy. This is however a difficult task.
My research goal is to develop novel strategies to treat breast and ovarian cancers that are resistant to common drugs. Many breast and ovarian cancers are no longer capable to correctly repair DNA when it is broken. This Achille’s heel can be used to eliminate cancer cells without damaging healthy tissues. My research team has identified a novel protein that help repair DNA and that is essential in these cancers. Our goal is to develop a drug against this protein and to test if we can use it to kill certain cancers that became resistant to current treatments.
Though survival for patients with advanced melanoma has improved over the last decade with the introduction of anti-PD-1 antibodies, half of patients treated with this therapy have disease that recurs. Both combination immunotherapies and single-agent anti-PD-1 antibodies are currently used to treat melanoma. However, combination therapies have higher responses but also higher toxicity rates. Currently, there are no definitive biomarkers that can predict which therapy choice is correct for metastatic melanoma patients.
This project is focused on understanding why patients are resistant to PD1-based therapies. We recently discovered that patients with more CD26 (a type of protein) found in the tumor’s immune cells are more responsive to treatment. These collective findings beg the question: What is the role of CD26 in the immune response to melanoma?
To answer this question we will study CD26 melanoma immunity using melanoma patients’ blood and tumor samples. This data will allow CD26 to be used as a biomarker in prognosis for patients treated with PD-1-based therapies, and allow for future studies for clinicians to use CD26 as a predictive biomarker to help select the appropriate treatment for a patient, i.e., combination or single-agent immunotherapy.
The role of CD26 activity in melanoma immune response will be defined by this project. Findings from this research will be the basis for future clinical trials to target CD26 in order to enhance immunity against tumors that are unresponsive to PD-1-based therapy in order to create new hope for patients with PD-1-refractory melanoma.
Funded by the Stuart Scott Memorial Cancer Research Fund
Using immunotherapy to treat advanced cancer has improved the outlook of cancer treatment in many cancer types. However, most of the gastrointestinal cancers, including pancreatic adenocarcinoma, do not benefit from such advances in immunotherapy. Upon further research, we have learned that dense non-cancer cells that surround these cancers not only prevent the chemotherapy drugs from reaching the cancer cells, but also prevent the tumor-targeting immune cells that allow immunotherapy to be effective. Research from Washington University show that a molecule called IRAK4 can control such a process and make pancreatic cancer respond better to chemotherapy while allowing immunotherapy to be effective. Based on the promising data from the laboratory, we propose a clinic trial of CA-4948, a drug that inhibits IRAK4 and has shown to be safe by itself, to be added to standard chemotherapy drugs to ensure safety. Then an immunotherapy drug will be added to the combination. We plan to collect blood and tumor samples from the patients receiving the combination of CA-4948, chemotherapy, and immunotherapy, to understand how these drugs change the tumor and components of the immune system in patients. In addition, we plan to further test this combination in animal models to test additional mechanisms that can improve immunotherapy in pancreatic cancer.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Acute myeloid leukemia (AML) in children is difficult to treat, and thus it is important to identify new and less toxic therapies. We have identified a protein called CD97 that is present on AML cells and is required for their maintenance. Because CD97 is present in multiple forms, we will determine which are required in AML cells. We also will make and test the ability of antibodies we have made against CD97 to eliminate AML cells. We expect our studies will not only reveal the role of CD97 in the development of childhood AML, but identify a potential new drug that may be used to treat kids with AML.
Lung cancer is a deadly disease. One common cancer treatment called immunotherapy boosts the body’s natural defenses to fight the tumor. However, while some lung cancer patients respond well to immunotherapy treatments, other patients do not respond to the therapy. This suggests that we need to find new ways to improve these treatments. Our research supported by the V Foundation aims to improve the body’s ability to fight lung cancer. We will study mechanisms to boost the effects of immunotherapy and we will test these new approaches using cancer models. This work has the potential to improve immunotherapy and expand the use of these treatments for larger numbers of lung cancer patients.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Ewing sarcoma is the second most common bone tumor in children, adolescents, and young adults. Patients who are diagnosed with a tumor that has not spread are usually cured. Those who are diagnosed with metastases (the tumor has spread from its initial location) are rarely cured despite decades of clinical trials and intensifying treatment regimens aimed at improving their survival. In preliminary animal experiments, we found that a drug called DFMO, already approved by the FDA for the treatment of African Sleeping Sickness, can inhibit Ewing sarcoma metastasis. We will test the hypothesis that DFMO acts by interfering with critical metabolic pathways in tumor cells, that it is safe to combine DFMO with chemotherapy, and that the combination of DFMO and chemotherapy will work better than chemotherapy alone in prolonging the lives of mice with Ewing sarcoma. Assuming we can show that the combination of DFMO and chemotherapy is better than chemotherapy alone in our mouse model, this will provide the rationale for future clinical trials testing the effectiveness of adding DFMO to standard chemotherapy regimens for Ewing sarcoma patients.