Funded in partnership with WWE in honor of Connor’s Cure
Brain cancer is now the leading cause of cancer deaths in children. A tumor known as high-grade glioma (HGG) is the deadliest type. Children with HGG are treated with surgery, chemotherapy, and radiation. They often enroll in clinical trials to try new treatments. Unfortunately, most children die within two years of diagnosis. Part of the problem is that HGG tumors develop ways to resist the effects of treatments. Our recent work using promising new glioma treatments has identified a pattern of steps that glioma cells use to develop treatment resistance. Using state-of-the-art genetic testing, we saw how HGGs at first responded to new therapies but then became resistant. Resistant HGGs showed increased levels of a protein called QPRT, which can use energy metabolites like NAD+ to protect cancer cells from the therapy designed to kill them. This suggests that by stopping the protein function, we could overcome treatment resistance. We want to achieve two aims: First: to see if QPRT is active in other commonly used treatments for HGG, and also if recurring childhood HGGs typically show high QPRT levels. Second, using tumor tissue that we cultured in the lab, we identified a drug that inhibits the NAD+ pathway and reverses treatment resistance. We want to test this drug in an animal model of treatment-resistant HGG to see if it can prolong survival. Together these aims would reveal a way that HGGs resist treatment and potentially show how a drug could block this action to overcome treatment resistance in these tumors.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Cure rates for children with cancer are improving, but cancer still comes back for many kids after finishing therapy. When cancer comes back it is more difficult to cure, and new treatments are needed to help these patients. The best way to develop new treatments is to treat patients with new therapies while collecting detailed information about how they tolerate the treatment and if it gets rid of their cancer – this is called being treated on a clinical trial, a research study designed to learn about how new treatments work for patients. These studies that involve new treatments are usually only offered at large hospitals that are connected to medical schools, so many patients are sent away from their homes to receive these treatments. Others choose to stay closer to home and not receive the newest therapies for their cancer. Often, there are research studies closer to home than their doctors realize. Getting this information to the doctors in our region would help make sure patients receive the newest therapies for their cancers while staying close to home. This grant would allow us to travel to nearby medical practices to tell the doctors about the new therapies that we offer at UVA as part of clinical trials, especially treatments that are being developed that allow the patient’s own immune system fight their cancer (called “immunotherapy”). Spreading this information will hopefully increase the number of patients that are treated on these research studies, and help cure more kids of their cancer.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Cancer in children is rare, accounting for less than 1% of all cancer cases in the USA. Clinical trials are used to determine the most effective and safest treatment for a disease and are commonly used in cancer treatment for children, adolescents, and young adults. The main reason that children are not enrolled on clinical trials is that there is not an open trial available. However, some nationally available trials could be opened faster when needed in local hospitals or cancer centers. Currently, the process is quite complicated and involves many steps. Our goal is to develop a “library” of available clinical trials that could be activated quickly on an as needed basis for children with rare tumors or with a cancer that does not respond to standard treatment. We will examine the barriers to rapid activation, educate the committees that are involved in clinical trial activation at our institution about the uniqueness of childhood cancer, and come up with a process for rapid clinical trial activation for childhood cancer at the Massey Cancer Center.
The Duke Cancer Institute and the College of Veterinary Medicine at N.C. State University formed a Comparative Oncology Consortium (COC), taking advantage of their expertise and national leadership in their respective disciplines and their geographic proximity. The goals are to collaborate in pre-clinical and clinical cancer research activities in order to advance our understanding of both cancer causation (a high incidence of specific cancers in specific dog breeds provides opportunities to identify new cancer susceptibility genes and environmental factors in cancer causation) and of behaviors and genetics of specific tumor types, as well as to coordinate clinical trials in humans and canines so that novel therapies can be tested in both settings, with information gained in one setting informing the other. In addition to response outcomes of these cancer therapies, the ability to use biomarkers and pharmacology in the canine models can be a novel addition to the characterization of these new cancer therapies and these insights could result in significant enhancements of clinical trial designs (including dosing, scheduling, and combination therapies) when these treatments are tested in human clinical trials. Cost savings and improved clinical trials design would help encourage pharmaceutical companies to use the canine models as part of the assessment process and would benefit the canine patients by giving them access to these novel therapies.
Project 1: My research interest is cancer genetics with an emphasis on clinically relevant questions that will improve our understanding of the cancer genetics of clinical phenotype and simultaneously improve patient care in oncology. I have extensive bench research experience in the fields of genome sequencing technology development, human genetic analysis through human genome sequencing and molecular assay development. My research benefits from the various innovations in genomic and genetic technologies that my group has developed.
Project 2: Based on a series of recent discoveries using cutting edge tools in genomics, we have (1) identified a new targeted way of treating metastatic gastric cancer and (2) pioneered a new way of determining how gastric cancer cells control normal cells in the surrounding stomach tissue.
Our overall goal for this project is to use single cell genomic sequencing to identify new drug targets by analyzing primary gastric cancers from metastatic patients.
Project 3: Based on a series of recent discoveries using cutting edge tools in genomics, we have (1) identified a new targeted way of treating metastatic gastric cancer and (2) pioneered a new way of determining how gastric cancer cells control normal cells in the surrounding stomach tissue.
Our overall goal for this project is to determine if our new discovery of a drug combination will improve the treatment of metastatic gastric cancers with the FGFR2 defect.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Our grant aims to develop drugs for altered forms of the protein MLL which arise in pediatric leukemia. Patients with leukemia harboring altered forms of MLL have very poor survival, highlighting the need for new approaches to treat these patients. The altered MLL proteins are highly dependent on the ability of one part of the protein to bind to DNA. We are developing drugs to block this binding. Our initial results support that this approach could be highly effective for treating this type of leukemia. Since this is a new way to treat the leukemia, it has the potential to be more effective than currently used drugs as well as less toxic. In addition, since this is a very different approach from existing drugs, it is likely that combinations of this new drug with existing drugs will provide unique benefits.
Funded in partnership with the Goldberg Family Foundation and in collaboration with the Gray Foundation
Individuals with BRCA1 or BRCA2 mutations have an increased risk of developing breast, ovarian, pancreas, prostate and other types of cancer. Tumors arising in these individuals are often sensitive to PARP inhibitors (PARPi) and this class of drugs has shown remarkable success in the treatment of BRCA1 and BRCA2-mutant tumors. Despite these successes, tumors frequently become resistant to therapy. Using functional genomic approaches, we will investigate mechanisms of resistance and identify novel genetic vulnerabilities that can be exploited by PARPi treatment. We will also investigate the immune response to BRCA-mutant tumors and explore ways to improve the ability of immune cells to recognize and kill these tumors. The ultimate goal of these studies is to improve outcomes for patients with BRCA-mutant tumors and to identify new groups of patients that can benefit from PARPi.
African Americans have the highest percentage of new cancer cases in the United States and the worst outcomes. Some people die from cancers that can be prevented or treated, simply because they are not aware of all of the treatment options. Cancer care can be very difficult because many times a patient has more than one doctor who is part of their care team. This can be scary and may make some people choose not to get cancer treatment, even if they can be cured. Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) wants to make sure that everyone has access to the best cancer care possible. To meet that goal, we will engage an African American Patient navigator (AAPN) – someone who is from the community who can help people learn about cancer, how to prevent it, what screening is required and what treatments are available. If someone diagnosed with cancer comes to WFBCCC for treatment and needs assistance, the AAPN will meet with them and work to help remove any barriers to care. The AAPN will also talk about clinical research that may be recommended as part of a treatment plan. Cancer research may improve outcomes for them or it may provide information that can help improve treatments for the next generation of cancer patients. Since African Americans get cancer more often, it is important to make sure they are represented in studies that look at new treatments and supports for cancer patients.
Clinical trials are important to improve cancer treatments and survival. Very few people are treated on cancer clinical trials and an even small number of those treated on a trial are African American. One way to solve this problem is to use specially trained staff to help cancer patients better understand clinical trials. These staff are called patient navigators. In this project, we will use patient navigators, one who is African American, to teach and support patients asked to be in cancer clinical trials. These navigators will work as a team to make sure that all African Americans who receive care at the Cancer Center are considered for cancer clinical trials. They will teach patients about clinical trials. They will also help them better understand the hospital system and give advice to patients who live far away and don’t have a car or place to stay when they come to their 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.
There is a low number of people involved in clinical studies. This is a national problem. This problem plays a part in poor health for people with cancer. It is even more of a problem for people of color who do not take part in clinical studies at the same rate as whites for several reasons. Some of these reasons include fear and not knowing about clinical studies. Also, some current and past research studies did not tell people of color the truth about the study and caused high rates of sickness and death in some cases. These reasons play a role in some people deciding not to take part in a study. Some people of color are not involved with clinical studies because they were not asked. Research teams may not ask people of color due to bias that they may not be aware of or concerns about trust. Studies show that most people who take part in a study do so because they were asked. The main reason people do not enroll in clinical studies is because they were not asked and did not know anything about it.
Studies suggest there is a need to teach research teams how to build skills in working with people of color. There is a need to build trust between patients and clinical staff as well as learn ways to increase the number of people of color enrolled in studies. The Just Ask: Diversity in Clinical Research Training Program works with patients, the community, and research teams to build skills and increase the number of people of color in clinical studies.
Manage Consent
To provide the best experiences, we use technologies like cookies to store and/or access device information. Consenting to these technologies will allow us to process data such as browsing behavior or unique IDs on this site. Not consenting or withdrawing consent, may adversely affect certain features and functions.
Functional Always active
The technical storage or access is strictly necessary for the legitimate purpose of enabling the use of a specific service explicitly requested by the subscriber or user, or for the sole purpose of carrying out the transmission of a communication over an electronic communications network.
Preferences
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
Statistics
The technical storage or access that is used exclusively for statistical purposes.The technical storage or access that is used exclusively for anonymous statistical purposes. Without a subpoena, voluntary compliance on the part of your Internet Service Provider, or additional records from a third party, information stored or retrieved for this purpose alone cannot usually be used to identify you.
Marketing
The technical storage or access is required to create user profiles to send advertising, or to track the user on a website or across several websites for similar marketing purposes.
To provide the best experiences, we use technologies like cookies to store and/or access device information. Consenting to these technologies will allow us to process data such as browsing behavior or unique IDs on this site. Not consenting or withdrawing consent, may adversely affect certain features and functions.
Functional Always active
The technical storage or access is strictly necessary for the legitimate purpose of enabling the use of a specific service explicitly requested by the subscriber or user, or for the sole purpose of carrying out the transmission of a communication over an electronic communications network.
Preferences
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
Statistics
The technical storage or access that is used exclusively for statistical purposes.The technical storage or access that is used exclusively for anonymous statistical purposes. Without a subpoena, voluntary compliance on the part of your Internet Service Provider, or additional records from a third party, information stored or retrieved for this purpose alone cannot usually be used to identify you.
Marketing
The technical storage or access is required to create user profiles to send advertising, or to track the user on a website or across several websites for similar marketing purposes.
