Grant Archive - Page 49 of 138

Donna Hammond, Ph.D.

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

Cancer survivors often continue to have certain side effects of anti-cancer drugs long after treatment has ended. Their hands and feet may feel numb, or they may feel unpleasant sensations in their hands and feet like burning. The simple touch of clothing or holding a cold can of soda may feel painful. Pin prick or paper cuts may hurt more than expected. These abnormal sensations are called chemotherapy-induced peripheral neuropathies (CIPN). They can seriously diminish the quality of life, and interfere with self-care and activities of daily living. Sixty-eight percent of patients report these abnormal sensations when asked 30 days after the end of anti-cancer treatment. Although the abnormal feelings may decrease over time, they can persist for months to years in as many as 30% of cancer survivors. Advances in diagnosis and treatment of cancer have increased the number of survivors to nearly 14.5 million. Of these, up to 4.5 million may continue to suffer CIPN long after their treatment has ended. There are no effective drugs for these survivors. We recently discovered that NIAGEN®, a type of vitamin B3 that increases levels of NAD+, can prevent abnormal sensations in a rat model of CIPN. Importantly, it can also reverse CIPN that persists after the last dose of paclitaxel. The goal of this study is to translate these laboratory findings to the clinic and the patient. Here, we will determine whether daily treatment with NIAGEN can relieve residual persistent CIPN in cancer survivors.

David Gerber, M.D.

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

While immunotherapy can sometimes result in dramatic and prolonged responses, it can also cause major toxicities. Immune-related adverse events (irAEs) are quite different than the toxicities seen with other cancer treatments, such as conventional chemotherapy. They occur when immunotherapy causes the patient’s own immune system to attack normal organs in the body. These toxicities may occur at any point in treatment, may be severe, and—of particular concern to cancer survivors—may be permanent.

irAEs remain poorly understood partly because immunotherapy research has focused almost exclusively on tumor biology, which is certainly relevant to immunotherapy effectiveness. However, we believe that toxicities irAEs have more to do with patients’ own immune systems. Our research team has expertise in cancer, immunology, and genetics. We have already collected clinical information and blood samples on hundreds of patients receiving cancer immunotherapy. With this information, we have identified some blood-based tests that may predict the future development of irAEs.

We now take this research to the next level by proposing genetic and functional tests to identify underlying predisposition to irAEs. Specifically, we will study DNA and RNA in blood samples from our existing patient cohort. If successful, our research could ultimately help (1) identify high-risk patients, (2) customize therapy, (3) tailor monitoring, (4) expand immunotherapy use, and (5) prevent toxicities.

Guang-Shing Cheng, M.D.

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

Hematopoietic cell transplantation (HCT) can cure cancer in many patients, but some survivors will develop a devastating complication called bronchiolitis obliterans syndrome (BOS). BOS causes debilitating scar tissue in the lungs. Patients with BOS can experience shortness of breath, lung infections and long-term breathing problems. Some patients will die from BOS. BOS is hard to treat because most patients are diagnosed with after permanent damage has been done. If we can diagnose BOS earlier, before patients have symptoms, we might be able to prevent suffering. HCT patients who have a condition called chronic graft-versus-host disease, in which donor cells attack the patient’s tissues, are more likely to develop BOS. Our study will enroll patients with chronic graft-versus-host disease and test whether a simple tool called a spirometer can detect the earliest signs of BOS. We will give study participants a handheld spirometer to measure how well a participant’s lungs are functioning. During the study, participants will use the spirometer every week at home. The spirometer connects to the participant’s smartphone. The results will be sent to the study team over internet. If the team sees that a participant’s lung function begins to decline, the participant’s doctor will be informed. We hope that this tool can help a patient’s doctor diagnose and treat BOS earlier. Our ultimate goal is to ensure that patients who survive cancer also thrive after their treatment.

Smita Bhatia, M.D., MPH

Funded by the Dick Vitale Pediatric Cancer Research Fund

Anthracycline chemotherapy is used to treat over 50% of childhood cancer, and has resulted in improving in survival, such that over 85% of children now survive 5 or more years after a cancer diagnosis. Unfortunately, heart failure is an unwanted side-effect of anthracyclines, and is one of the leading causes of death in children cured of their cancer. Childhood cancer survivors are at a 5-15-fold higher risk of serious heart problems compared to the general population. The risk of heart failure increases with anthracycline dose, but the risk differs from child to child.  Several studies have looked at the cause of heart failure at the DNA level. However, it is important to take this investigation to the next level, that is, truly understand the basic causes of at heart failure caused by anthracyclines. We propose to do this in a large study across 141 childhood cancer hospitals, where we are collecting blood samples from 300 childhood cancer survivors who have developed heart failure and 300 childhood cancer survivors who did not develop heart failure. We will use this information to get a deeper look at how anthracyclines cause heart failure. We hope that this will help us identify patients at highest risk, providing guidance in developing new ways to prevent and treat this unfortunate complication.

Saro Armenian, DO, MPH

Funded by the Stuart Scott Memorial Cancer Research Fund

Stem cell transplantation is an effective way to treat patients with blood cancers. However, this treatment can cause short- and long-term side effects. These side effects may affect quality of life and increase risks for other diseases. Doctors must balance these risks with the potential for stem cell transplant to cure patients. A risk-prediction model can help with such decisions, but current models are inadequate. Risk-prediction models are often based on a patient’s age, but people of the same age in years may not be alike in terms of underlying health. Underlying health can be estimated with various “biomarkers.” Our proposal is designed to identify a new biomarker that shows whether a patient is fit for stem cell transplant. We are studying clonal hematopoiesis of indeterminate potential (CHIP), a group of genes that indicate the health of a patient’s blood cells. Our hypothesis is that patients with CHIP in the blood before stem cell transplant will have poor outcomes after transplant. To test this, we will use a large collection of blood samples taken from blood cancer patients before stem cell transplant. We also have information about each patient’s health after transplant. We will use DNA sequencing to measure CHIP genes in the blood samples. We will use statistics to compare CHIP in the samples with patient health after stem cell transplant. If these correlate, it will show that CHIP is a good biomarker for use in a risk-prediction model. This will help doctors make personalized decisions that improve the lives of blood cancer patients.

Jaime Modiano, Ph.D., D.V.M.

Funded by the Dick Vitale Gala

Sarcomas are cancers of bone and connective tissue. These cancers are not very common in people, but they are no less serious than other, more common cancers. One reason there are few new treatments for sarcoma is that their rarity makes it difficult to obtain material for study. To overcome this, we have studied sarcomas in animals, and especially in pet dogs. Dogs share our environment and their risk to develop cancer is about the same as it is for humans. But unlike people, dogs develop sarcomas very commonly. Over the past twenty years, we have found how sarcomas of dogs are like sarcomas of people. This creates opportunities to develop new sarcoma treatments in dog “patients”. For this project, we are studying how we can activate the immune system to kill sarcomas – and specifically bone cancer. Our strategy starts with a virus that infects and kills cancer cells. Because this allows the immune system to recognize the tumor, we can then add a protein to enhance the potency and duration of this immune response. The idea is that the treatment will eliminate the primary tumors and prevent or delay cancerous spread to other organs. We will test our strategy in the laboratory and in dogs with bone cancer in a clinically realistic setting, which will provide avenues to move our findings more quickly to human patients who will ultimately benefit from this therapy.

Yong Zhang, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Cancer cells contain a set of highly active proteins. They can add small groups to a series of target proteins. These uncommon additions are often linked with tumors found in breast, liver, and other tissues. To date, it is still unclear how those aberrant additions cause cancer. To answer this question, it is crucial to know all the interaction targets for the additions in cancer cells. But no method has been made available to resolve this key issue. In this project we are aimed to create an innovative platform to achieve this goal. Our research plan will use chemistry and biotechnology to make new tools for target identification. A particular member in this group will be chosen for this work. Because it shows much higher activities in diverse types of cancer. The full range of interacting targets for this protein will be clearly determined. Moreover, the patterns and levels of such interactions in cancer cells can be precisely measured by our creative approach. These findings will unveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this work will advance our understanding of cancer. Importantly, it will foster the development of new approaches for cancer detection and treatment.

Yuliya Pylayeva-Gupta, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Pancreatic cancer is a very aggressive disease. It is the 3rd leading cause of cancer deaths in the USA. Only 8% of patients who can undergo surgery will survive past five years. Late diagnosis and lack of good treatment options are some of the reasons for this outcome. Recent progress in cancer immune therapy showed effect in cancers such as relapsed leukemia and metastatic melanoma. Unfortunately, immune therapy was not effective in patients with pancreatic cancer. One explanation for this result is that pancreatic cancer blocks immune responses against cancer. Thus, understanding how cancer promotes immune suppression is vital to our ability to treat this deadly disease. Our initial work has revealed that B cells promote growth of pancreatic cancer and resistance to immunotherapy. However, it is not clear how B cells promote cancer growth, and how targeting these cells can benefit patients. We propose to understand how B cells function in pancreatic cancer. The goal of this research project is to find new targets that can block immune suppression in pancreatic cancer. Using both mouse models of pancreatic cancer and patient samples, we hope to identify B cell based targets in pancreatic cancer. We ultimately hope to translate our findings into effective therapies that may also work with existing immune therapy treatments.

Karen Winkfield, M.D., Ph.D.

Funded by the 2018 Victory Ride to Cure Cancer

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.

Carrie Lee, M.D.

Funded by the 2018 Victory Ride to Cure Cancer

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.