Funded by the 2019 Wine Celebration Fund a Need for Canine Comparative Oncology
Sarcomas are malignant cancers that form in bone and soft tissues (muscle, cartilage, nerves) in many species. Sarcomas are rare and often affect children and teenagers. Outcomes have not changed much in the last 10 years. New treatments are needed to better cure these tumors. Because sarcomas are not common in people, it can be hard to test new treatments. Pet dogs commonly develop sarcomas, and their tumors behave like human tumors. Pet dogs with sarcoma give usa chance to test new treatments that can help both dogs and people.Radiation therapy is commonly used to kill sarcoma cells in dogs and humans but it cannot cure tumors by itself. Radiation therapy can also causean anti-cancer immune response, where the body’s own immune cells kill tumor cells for a short time. In this study, we are exploring a new way to use the immune system to work with radiation therapy to destroy sarcoma cells. We have invented a designer drug specifically for dogs that “kick-starts” the anti-cancer immune response. We expect that this drug will help us improve outcomes for patients with sarcomaswhen radiation therapy is used. We will test this expectation in the laboratory and in pet dogs with sarcomas that need treatment.This project will help uslearn to use a drug like this in people with sarcomas that need radiation therapy.
The goal of “Campaign to Improve Access to Clinical Trials” at the University of Arizona Cancer Center (UACC) is to increase the clinical trial access to a diverse population in Arizona. Dr. Chalasani, Breast Cancer Disease Oriented Team Leader, will oversee the campaign to improves access by involving the breast multidisciplinary team, patient navigators and physician liaisons to develop educational materials and outreach programs. Patients and community physicians will be targeted through proposed outreach programs by developing targeted educational materials. Materials and training will be provided to introduce and educate about clinical trials to patients early by various members of their cancer team. The goal of this campaign is to become a model for other disease teams and cancer centers to implement to improve clinical trial enrollment.
This application focuses upon the need to develop new therapies for stomach cancer, which is the 3rd leading cause of cancer mortality in the world. In our laboratory’s prior studies, we described the patterns of disruptions in the genome (or DNA of the cell) that develop in the stomach cells which become cancerous. The overall hope for this work is that finding the genetic causes of cancer can be a source of development of new targets for guiding cancer therapy. The primary way to try to use genomic understanding of cancer to guide therapy has been to find specific genes which are aberrantly activated in cancer. However, to date, approaches to use this approach to guide therapy for stomach cancer has been largely disappointing despite individual successes. Therefore, this new research program supported by the V Foundation and the Gastric Cancer Foundation aims to develop alternative approaches to use our understanding of the gastric cancer genome to guide development of new therapies. Instead of focusing on the genomic alterations that impact individual genes, we are now pivoting to more broadly evaluating the patterns of genomic alterations and the classes of instability or genomic disruptions that occur in cells. We have developed new approaches to classify the types of genomic disruptions that are characteristic of gastric cancer and then directly connecting these patterns to possible new therapeutic targets. We believe that this work may serve as a critical foundation for novel development of therapies for these deadly cancers.
Funded by 2020 Kay Yow Cancer Fund Final Four Research Award
Since the mid-1960s, New Orleans has had a majority AfricanAmerican (AA) population, many of whom are poor and uninsured. This, along with a lack of communication, misunderstanding of clinical research and limited funding for education and outreach, has led to a lack of access to clinical cancer research trialsamong this demographic.
The goal of this program is to assist in the enrollment of cancer patients and those at risk for cancer into clinical research trials, with particular emphasis on outreach, recruitment and enrollment of minority patients.
Pivotal to this effort is a patient navigator with extensive training in cultural competence who will be assigned specifically to clinical research. In addition to assisting enrollment in trials at our clinical sites, the Navigator will also use Tulane’s established relationships with community organizations, community leaders, area physicians and affiliate sites to help educate minorities about clinical research.
The Navigator will identify and approach prospective study patients;build a relationship with them, their caregivers and family members;and guide them through the enrollment processwhile serving as an essential link between the patient and the study team.
Funded in partnership with WWE in honor of Connor’s Cure
Hepatoblastoma (HB) is the most common cancer of the liver in children. Although usually very curable, some HBs have less than 20% survival. About 80% of these have changes in a protein known as b-catenin. Many also show abnormal regulation of another protein called YAP. Together, these are the most common changes in HB. Mice develop HB if a mutant form of b-catenin, termed D(90) and a mutant form of YAP known as YAPS127Aare expressed together in the liver although neither one alone causes tumors. 5-10% of HBs also contain mutations in a third protein, NFE2L2, that normally prevents certain types of DNA damage. In initialstudies, NFE2L2 mutants sped up tumor growth in response toD(90)+YAPS127A. Unexpectedly, NFE2L2 mutants caused tumors when present in livers with eitherD(90) or YAPS127A. Thus, any two combinations of thesemutations cause cancer. This research will ask exactly how each pair of mutant proteins alters tumor growth. It will also identify the small number of common changes that underlie these tumors. This has previously been impossible because the differences between normal livers and tumors is so large. Identifying the genes shared by different mutant combinations should make this easier. Our proposal is innovative because it will find the most important changes that cause HB. It is translationally important because knowing these changed genes may uncover new ways to treat HB and other pediatric and adult cancers.
Funded in partnership with Miami Dolphins Foundation
It is estimated that 1 in 8 women will be diagnosed with breast cancer in the US. During the last decades, breast cancer survival rates have greatly improved, mainly due to factors such as earlier detection and a better understanding of the disease. There are at least five different type of breast cancer. In this proposal, we will investigate one of the breast cancer subtypes, called estrogen receptor positive (ER+) breast cancer. ER+ breast cancer needs the estrogen to grow.Estrogen is a hormone that is important for sexual and reproductive development, mainly in women. ER+ breast canceraccounts for 70% of breast cancers and is typically treated with drugs designed to slow or stop the growth of cancer that uses estrogen to develop. Although thistype of therapy has been shown to reduce the risk of relapse and death from breast cancer,one third of patients develop resistance. This resultsin the spreading of cancer cells to other organs, known as metastasis. Thus, there is a critical need for identifying new treatments for patients who develop resistance to current therapies. The focus of this proposal is to understand the mechanisms of resistance to therapy and to overcome resistance by using a novel therapeutic approach. This is the next step towards our overarching goal, which is the identification of new therapeutic opportunities for the treatment of patients with aggressive breast cancer.
Funded in partnership with the Kansas City Chiefs Football Club
The immune system can destroy cancer cells. This is being taken advantage of in cancer therapy, withscientists trying to find ways to activate the immune system to better kill cancer cells. One therapy involves theinfusion of immune cells named natural killer (NK) cells. This therapy works well for some types of cancers.However, there has been limited success with this therapy against most tumors. The ultimate goal of our research is to increase the ability of this therapy to work against more cancers. One method proposed formaking NK cells better at killing cancer cells is treating the cells with activating signals that are termed IL-12, IL-15, and IL-18. We show that this makes the NK cells express proteins that affects the ability of the cells to killcancer cells.This leads us to think that IL-12,15, and18 treatmentalters NK cells in a way that can be good for the treatment of some, but bad for other, types of cancer.This is of highconcern because IL-12,15,18 treatment is proposed as a way to enhance NK cell treatment of cancers and isbeing tested in patients. Therefore, it is critical we determine how IL-12,15,18-treated NK cells affect the growth of different types of cancer. Here we propose to determine how IL-12,15,18-treatment, and the proteins this treatment induces on NK cells, alters the ability of NK cells to kill cancer in mouse models.
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.
Funded in partnership with the Morris Animal Foundation and the Wine Celebration Fund-A-Need
In 2012, Morris Animal Foundation launched its Golden Retriever Lifetime Study primarily to explore the risk factors related to cancer in golden retrievers. The Study has been following 3,044 dogs throughout their lives, collecting wide-ranging data on each animal each year, including environmental exposures, behavior, medical diagnoses, medications, diet and more. Golden retrievers were selected for this study because they are diagnosed with cancer at a much higher rate than most other breeds of dogs, and some of the most common cancers in golden retrievers are closely related to common human cancers.
This grant relates to genomics of our enrolled Study dogs. We will first test DNA samples from all of the dogs. We will be looking for small variations in hundreds of thousands of places along the DNA strands. Some variations may imply that a dog has a greater risk of a certain cancer type or one of the other diseases we are documenting. Similar studies are done for humans, but the advantage in dogs is that such information might ultimately be used in breeding programs to reduce the occurrence of cancer in the first place.
A second aspect of the grant will focus on biopsy specimens. We receive biopsy specimens from many of the cancers diagnosed in our Study dogs. We will be conducting a very detailed analysis of DNA, called sequencing, in these cancer tissues. Cancers occur due to changes in the DNA, called mutations. This study will allow us to determine which mutations are occurring in certain cancers that have similarity with those occurring in human patients. These include lymphoma (a cancer of white blood cells), osteosarcoma (bone cancer), and hemangiosarcoma (cancer of blood vessels). This information may lead to further studies on how to prevent and treat these cancers in both dogs and humans.
Funded in partnership with the Morris Animal Foundation and the Wine Celebration Fund-A-Need
In 2012, Morris Animal Foundation launched the Golden Retriever Lifetime Study primarily to explore the risk factors related to cancer in golden retrievers. The Study has been following 3,044 dogs throughout their lives, collecting wide-ranging data on each animal each year, including environmental exposures, behavior, medical diagnoses, medications, diet and more. Golden retrievers were selected for this study because they are diagnosed with cancer at a much higher rate than most other breeds of dogs, and some of the most common cancers in golden retrievers are closely related to common human cancers.
The data being collected by the Golden Retriever Lifetime Study is freely available for academic research via the Morris Animal Foundation Data Commons. The goal of the current project is to augment the Data Commons with high-resolution genotype data on each of the dogs and, eventually, complete DNA sequence data on all of the dogs diagnosed with cancer, along with a suitable number of other dogs as controls. As the genotyping and sequencing is completed, Morris Animal Foundation will perform preliminary data validation and analysis, and then incorporate the data into the Data Commons, where it will be available to everyone with an account. This will enable researchers from institutions around the world to participate with us in the effort better understand canine cancer as well as inform human cancer research.
Morris Animal Foundation Data Commons accounts can be requested by anyone involved in academic research by completing the registration form on the Data Commons website.
