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.
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.
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.
V Scholar Plus Award – extended funding for exceptional V Scholars
Cancer cells contain aset 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 aberrantadditions cause cancer. To answer this question, it is crucial to know all the interactiontargets for the additions in cancer cells. But no method has beenmade 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 particularmember in this group will be chosen for this work. Because it showsmuch higher activities indiversetypes of cancer. The full range ofinteracting targets for this proteinwill be clearly determined. Moreover, the patterns and levels of such interactionsin cancer cells can be precisely measured by our creative approach. These findings willunveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this workwill advance our understanding of cancer. Importantly,it will foster thedevelopment of new approaches for cancer detection and treatment.
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.
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.
V Scholar Plus Award – extended funding for exceptional V Scholars
Cure rates for childhood leukemia have considerably improved in the last few years. Despite this, there are certain sub-sets of leukemia that do not respond well to current therapies.Currently used treatments are often extremely aggressive and non-specific, leading to significant debilitating effects in these patients. The overall objective of this application is to validate exciting new therapeutic targets that we have identified in high-risk subsets of AML using genetic and chemical approaches.
V Scholar Plus Award – extended funding for exceptional V Scholars
More than 40,000 American women die of breast cancer each year. One out of every eight women in the U.S. will develop invasive breast cancer during their lifetime. In 70% of these women, estrogen and estrogen receptor α (ERα) are key players in breast cancer diseases. Keeping this endocrine signaling function low by endocrine therapy is the best treatment right now. Yet, after 5 years, hormonal treatment stops working in more than 30% of these patients and the disease returns. Because hormone resistance is still a challenge, there are few effective therapies for these patients. We plan to study estrogen and ERα related to hormone resistance.
ERα binds DNA elements that regulate gene expression. These elements are very important in cancer development and progression. When these elements lose control, breast cancer becomes resistant to hormones. Thus, if we can find ways to understand and correct these elements in hormone resistant cells, we can find cures for ERα-positive breast cancers. The goal of this project is to understand how ERα controls DNA elements. We will identify markers to measure the presence and progression of breast cancer. Our research results may lead to new therapies that target this disease. Discoveries from this project may help with treating other cancers and may be useful for other research fields.
