Zhaoming Wang, PhD

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

Survivors of childhood cancer are at high risk of late health problems related to cancer treatment. Our early work suggested that health problems differ among survivors based on social-economic status like level of education, household/personal income, and the neighborhood in which they live. In the proposed research, we will describe and measure differences in health problems among childhood cancer survivors based on the social-economic status. We will focus on common health problems including obesity, high blood fat levels (triglycerides or cholesterol), abnormal blood sugar control, high blood pressure, heart muscle weakness, and heart attack. We will use stored blood samples and data already available from the St. Jude Lifetime Cohort Study to study biologic changes that may predict a survivor’s risk of health problems and links to social-economic factors. We hope that the results of this work will help identify survivors at higher risk for health problems and guide new research aiming to reduce, reverse, or prevent the harmful effects of social-economic factors on health problems after treatment for childhood cancer. 

Ulrike Peters, PhD

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

Colorectal cancer starts in the large intestine. It is the second leading cause of cancer death in men and women in the US. Alaska Native people have among the highest rates of colorectal cancer in the world. Alaska Native people also die more often of this disease than any other racial or ethnic group in the US. The reasons for these health disparities are not fully understood.  

Almost no research exists on molecular changes in Alaska Native colorectal cancer tumors. In this study, we will look at the genes expressed in these tumors. Genes code for proteins which support normal cell function. Changes to genes may result in abnormal growth of the cells resulting in cancer. Studying gene expression tells us which genes in the tumor may be causing the cancer and will help us understand more about the patterns of gene expression among Alaska Native colorectal cancer patients. We will also examine if tumor gene expression can tell us which patients will live longer with their cancer. 

This research will help to identify colorectal cancer patients with aggressive disease at diagnosis. This could help to guide clinical decision making and improve disease outcomes. Also, this research may tell us if Alaska Native colorectal cancer patients might benefit from available or new treatments. 

Jennifer Doherty, PhD, MS

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

Ovarian cancer is a leading cause of cancer death among US women, with about 50% of women dying from their disease within five years. Treatments including surgery and chemotherapy are meant to cure the cancer, but in about 50% of women, the cancer will come back 

Black and Hispanic women are more likely to stop treatment early, and to die from their disease than non-Hispanic white womenThese differences are referred to as race/ethnic disparitiesThere are many reasons for disparities, including differences in access and quality of medical care. Black and Hispanic women are also more likely to have other health conditions (i.e. comorbidities)like heart disease or diabetes, when they are diagnosed with ovarian cancer. These comorbidities may change a patient’s ability to tolerate treatment, and in turn, may reduce their survivalComorbidities may also change the biology of the tumor. Looking at tumor markers may provide information on response to treatment and survival of the patients.  

The goal of this project is to understand race/ethnic disparities in ovarian cancer treatment, recurrence, and mortalityIn this project, we will examine how comorbidities and tumor markers differ in a diverse group of ovarian cancer patients. This study will take place using data from the Kaiser Permanente Healthcare systemThis research project will provide information for doctors about how health conditions can affect a woman’s response to treatment, so that she can get better cancer care, and help to reduce disparities in ovarian cancer treatment and outcomes.

Ann Partridge, M.D.

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

People who have been treated for cancer are not only at risk of cancer returning, but also at risk of long term side effects of their treatments some of which may threaten their life, including heart disease and other cancersMedical teams are always searching for new ways to identify and reduce these risks. Some people will develop changes in their blood cells called “Clonal Hematopoiesis (CH) and people with these changes have recently been found to be at higher risk of developing serious problems such as cancer and heart attacks and dying.  CH is found more in older than younger people and more commonly in people who have been treated for cancer.  We don’t know how common CH is in cancer survivors, who is at risk, when it develops and when and if we should be looking for it.  But we are finding it more commonly with genetic tests that are being done as a part of their care. Our team hopes to provide answers to these questions by looking for CH in a group of women who were treated for breast cancer at a young age and agreed to give us blood samples and let us follow them over time.  We will do special testing to find CH in their stored blood and see how it is different in different women, and changes over time.  We will also ask them how they might feel about learning about CH results if they had CH, how learning about these risks that might affect them, and what they might need to support them best to help them to manage these risks.  We hope this research leads to findings that can be used to understand this problem better and to improve how we take care of cancer survivors both now and in the future.

Elli Papaemmanuil, Ph.D.

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

Leukemias represent cancers of the blood and are caused by genetic changes (mutations) in our blood cell that drive uncontrolled cell growth. Cancer survivors are more likely to develop leukemia than the general population. Traditionally this was thought to be a consequence of toxicity from the treatments used to fight their cancer, which leads to the development of therapy-related myeloid neoplasm (tMN) one of the most deadly and challenging to treat cancers. However recent studies show that leukemia associated mutations can be found many years before cancer diagnosis and interestingly, these blood mutations can also be seen in healthy people who never develop leukemia. This is phenomenon is called clonal hematopoiesis (CH). Our group has shown that CH is frequent in cancer patients and we find that cancer treatment may promote growth of cells carrying such mutations. To understand the effects of cancer treatment in patients that carry such mutations and how this dictates subsequent progression to leukemia, we propose to study a total of 45,000 cancer patients at time of cancer diagnosis. This will identify individuals with CH at time of diagnosis. We will then follow up patients and study the effects of oncologic therapy to analyzed for the presence of CH and study the effects of distinct cancer treatments on CH. Our study will help us understand tMN and guide the development of interventions to prevent tMN.

Kevin Krull, Ph.D.

Year one is partially funded by UNICO in memory of Toni Alongi

Survivors of childhood leukemia (ALL) who are treated with chemotherapy develop poor cognitive skills (e.g. attention, speed of thinking, reasoning). These poor cognitive skills cause problems with school, work and peer interactions. The survivors also display abnormalities on brain imaging. We demonstrated that fluid collected during a spinal tap (i.e. cerebrospinal fluid [CSF]contained markers of brain injuryHowever, our initial study was too focused on specific brain cells. We could not identify the cause of the brain injury. Thus, we want to conduct another study to examine many more protein markers before and after chemotherapy treatment. 

We will use an advanced process to identify over 4,000 proteins in the CSF. This will permit us to determine the cause of the brain injury. We will compare the proteins to sex and age of the survivors. We will also compare the proteins to the treatments the survivors got. Finally, we will compare the change in proteins to brain imaging and cognitive testing. 

CSF samples from a recently completed trial have been collected and frozen at −80°C so they will not decay. The brain imaging and cognitive testing is currently being completed as part of an institutionally funded protocol. For the current project, we will process the CSF samples and link them to adverse events and clinical outcomes 

With this comprehensive approach, we will identify which survivors are at greatest risk, and identify targets to prevent brain injury in future clinical trials. 

Norah Lynn Henry, M.D., Ph.D.

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

Aromatase inhibitors (AIs) are important drugs for treating breast cancer. These drugs lower estrogen levels and reduce the chance that a woman will die from cancer. However, about one in five patients stops taking the drug early because of aggravating muscle and joint pain. Stopping the drug too soon can increase her risk of her cancer coming back. We do not know why women develop this pain, but it might be due to very low estrogen levels. We also do not know how to prevent the pain. Oxylipins are fat particles in the body that can increase or decrease pain. We believe that when a woman is treated with medicine that lowers her estrogen levels, that leads to more fats that cause pain. By also taking omega-3 pills, we believe that women instead will have more fats that decrease pain. This will allow her to continue to take the AI medication. To address this question, women who are starting to take an AI will also take either omega-3 pills or olive oil pills. We will ask if they develop pain and also check the levels of fats in their blood.  Through this study we will find out if omega-3 pills prevent this side effect, and will learn more about how the AI medicine causes the pain. Knowing more about why women get this bothersome pain and how to prevent it will allow doctors to better treat patients and will allow more women to continue taking this life saving medication.  

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 theseup 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®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 biologywhich 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.   

Wnow 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 problemsSome patients will die from BOS. BOS is hard to treat because most patients are diagnosed with after permanent damage has been doneIf 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 functioningDuring 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 declinethe 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.  

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