Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive type of malignant B-cell tumor. Despite progress in lymphoma treatment, up to 40% of patients will ultimately succumb to their disease. Chimeric antigen receptor (CAR) T-cells (CAR-T) are immune cells from patients where a patient’s own white blood cells are isolated and engineered to target and kill tumor cells. CAR-T cell therapies demonstrated an entirely new paradigm for cancer therapy and produced unprecedented initial responses in patients of relapsed or refractory DLBCL. However, our group and others recently observed that over half of patients on CAR-T therapy eventually had disease relapse and fatal progression due to development of resistance. Thus, there is an urgent need to improve the efficacy of response and delay or prevent CAR-T therapy resistance. To tackle this major obstacle, my group has developed sophisticated models and expertise to develop a novel strategy to target the tumor in a more precise, personalized manner to overcome chemo-, targeted- and CAR-T therapy resistance. Ultimately, we will rationally design and test the improved and safe combinations of CART with the newly discovered inhibitor for DLBCL therapy. The outcomes of this study have broad applicability 1) improve the current standard of care by overcoming refractory and relapsed DLBCL current therapy resistance, 2) enhance the CAR-T therapy efficacy, and 3), we anticipate, can be readily translated to improve quality of life and/or length of life and has immediate impact on DLBCL patient care.
The low number of minority populations in clinical trials leads to higher mortality in these groups. It is important to address these inequities in order to address these cancer disparities. By developing a program that addresses the needs of patients, clinics, institution and communities, we hope to support minority patients seeking care at DCI to lower the barriers to accessing life-saving cancer clinical trials.
North Carolina (NC) has the largest American Indian (AI) population east of the Mississippi River. Yet, we do not know much about the health and health care of AIs in NC. We do know cancer is their number one cause of death. We need to better understand cancer and cancer-related needs in this group to reduce the burden of cancer. Three NC cancer centers joined together in 2021 to learn more about how to help AIs with cancer. We will study how cancer of the liver and stomach affects American Indians in NC. And we want to find and create resources for our AI community. First, we will use the NC Cancer Registry and health insurance files to learn more about how and where AIs in NC get cancer care and any potential disparities. We will then have a community event to test for and treat the top cause of stomach cancer. Lastly, we will educate about liver and stomach cancer to help prevent them. This work will help AIs in NC by showing what the greatest needs are and the opportunities for better care. The long-term goal is to improve cancer outcomes in all AIs.
Head and neck cancer is deadly because there are no effective drugs. Cisplatin is a commonly used drug for cancer treatment. However, patients with head and neck cancer usually develop resistance to this drug, which eventually leads to death. Although cisplatin can effectively kill most cancer cells, it is less effective in killing a specific type of cancer cells called cancer stem cells, which are responsible for the regrowth of the cancer after cancer therapy. Accordingly, inventing a new drug that can effectively kill cancer stem cells will improve patient survival. However, no drugs are available for killing cancer stem cells. Identifying key players maintaining cancer stem cell growth will help develop more effective drugs. Recently, we found a protein named FOSL1 is required to maintain cancer stem cell growth in head and neck cancer. However, the reason why FOSL1 keeps cancer stem cells growing is not fully understood. We also found a drug that can block FOSL1 function to prevent cancer stem cell growth. However, the efficiency is low. To increase the treatment effect, we developed a more potent compound based on this drug that can more effectively kill cancer stem cells 100 times in head and neck cancer. Our goals are: 1) using this compound to explore why FOSL1 can maintain cancer stem cell growth; 2) determine whether this compound can overwhelm cisplatin resistance using animal models. The knowledge obtained in this study will lead to developing more effective drugs to improve head and neck cancer patient survival.
Clinical trials are used to test new cancer treatments that may improve patient survival. Black or African American (AA) patients are less likely to be treated in a clinical trial than White patients. One way to try to reduce this inequality is to use specially trained staff to help people with cancer better understand clinical trials. These staff are called patient navigators. In this project, we will use patient navigators to teach and support patients with cancer and help them overcome barriers to joining clinical trials and gaining access to new treatments. These navigators will focus on making sure all Black/AA patients with endometrial cancer or prostate cancer who receive care at the Cancer Center are considered for cancer clinical trials. In addition to teaching patients about clinical trials, the navigators will also help them better understand the hospital system and make and keep appointments. They will assist patients who live far from the cancer center with travel and with finding a place to stay when they come for appointments. They can connect patients to finance counselors, social workers, and other helpful community services. To understand if the project is a success, we will compare the total number of patients, by race, treated on cancer clinical trials before and after the project. We will also study why patients chose not to be on clinical trials even when they are eligible. This information will help us design new projects in the future.
Cancer is a leading cause of sickness and death around the world, with limited treatment options available for people whose disease has progressed or spread. While new treatments have improved how long people can live with cancer, lifespan for those whose disease has spread has seen far less improvement. One reason for this is the cancer’s ability to become resistant, or “immune,” to treatment. A new method of treating cancer, called precision oncology, uses molecular testing to not only understand how and why a tumor grows, but also how it can begin to become resistant to treatments that may have once worked.
One challenge, however, is that access to this molecular testing is not always available to all groups of people. This unequal access, based on race and other factors, can have a measurable impact on cancer patients’ lives — in a recent study, black patients were 38% less likely to receive this type of testing compared to white patients. Through our research, we hope to change this to create a more equal approach to cancer treatment regardless of race or other factors. To do this, we will create a high quality molecular testing program in the DC region, with particular attention to communities in need of more equal access to these treatment approaches. By including all racial groups more equally in this research, we will also be able to better answer future research questions in a way that does not exclude any groups of people.
Funded by Hockey Fights Cancer™ Powered by the V Foundation
Meningiomas are the most common intracranial tumor in adults. While most meningiomas can be successfully treated with surgery, there are a significant proportion of cases that require the addition of radiation therapy to delay tumor recurrence. However, our current methods of selecting which patients should be escalated for radiation after surgery remain relatively imprecise, especially for intermediate-grade meningiomas that can behave in a highly variable manner. Molecular profiling, specifically DNA methylation of meningiomas has proven to be an effective and efficient method of providing additional information on these tumors that can be used to better predict whether they will or will not recur after surgery. However, whether a similar set of molecular signatures exist to predict whether a meningioma of any given patient will respond to radiotherapy after surgery remain to be determined. This V Foundation grant will enable us to 1) develop a clinically important predictor using specific molecular signatures of any given patient’s meningioma to tell us whether their tumor will respond to radiation, 2) test this predictor through a novel, real-time, molecular-pathology informed clinical trial, and 3) determine if the same signatures that can prediction response to radiotherapy in the tumor tissue can be used to non-invasively provide the same information through a simple blood test. Results from this study have the potential to dramatically improve the way we treat patients with meningiomas and will represent a significant shift forward in the field of neuro-oncology.
Cancer care can be tough to navigate. Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFBCCC) wants to make sure all patients can access the best cancer care as easily as possible. Sometimes the best treatment outcomes are achieved by joining cancer research studies. To be sure treatments studied in cancer research are reliable and consistent for all patients, it is important that all groups are represented. African Americans have the highest percentage of new cancer cases in the U.S. and the worst outcomes, yet are less likely to be represented in research. Due to language and cultural barriers, Hispanic patients also have low research participation rates. Adolescents and Young Adults have the lowest research participation rate of any age group. It can also be harder for patients who live outside of the city to get cancer treatment because of where they live. To help ensure all groups are included in studies, AHWFBCCC created a population health navigator (PHN) program to help community members learn about cancer, how to prevent it, what screening is required, and what treatments are available. If someone is diagnosed with cancer, the PHN can help to remove barriers to care and help patients learn about the benefits of cancer research. With PHNs, AHWFBCCC hopes to increase research participation so that all can be represented.
Funded by the Dick Vitale Pediatric Cancer Research Fund
We study a set of bone cancers that affect children and young adults. The treatment for these cancers has remained the same for the last 40 years – combinations of toxic medicines known as chemotherapy, followed by surgery or radiation to remove what is left of the cancer. While this strategy cures some patients, far too many children continue to die from these cancers. We believe we have found two specific weaknesses in these tumors: problems in their ability to repair damage to their DNA and a survival signal in a special pool of cancer cells known as “residual disease”. Through this research, we hope to bring new therapies to patients and cure more children with these bone tumors.
Funded by the Dick Vitale Pediatric Cancer Research Fund
One major challenge in treating any type of cancer is resistance, or when a cancer stops responding to a certain type of drug or therapy. Some cancer cells may become resistant my changing the way they read and write their DNA, or the genetic blueprint in the cell nucleus. Other cells may change the way proteins are expressed on the surface, which can change their shape or ‘stickiness’ and ability to move in the body. When doctors can understand exactly how cancer cells become resistant to a certain drug, they can sometimes combine two or more drugs together to overcome this.
For some new classes of drugs, we have not even begun to explore how cancer cells might become resistant. One of these classes is nanoparticle drugs, which usually involves bringing together molecules like fats or polymers to help delivery drugs into certain cells. The goal of this research project is to identify the ways that pediatric cancer cells can become resistant to nanoparticle drugs, and find new drug combinations that are more effective and less toxic to children with cancer. Many lab-based studies of nanoparticles are performed in common cancers of adulthood such as breast cancer, and this has led to new treatments in the clinic, but there have been very few studies of nanoparticle drugs in childhood cancer. Currently, there is only one nanoparticle drug approved for use in children. By studying resistance to nanoparticle drugs in a deadly childhood brain tumor, we can take the first step towards a new clinical treatment for these children.
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