Lung cancer is the leading cause of cancer death in the US and worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. A subset of these cancers has a “driver” gene mutation the epidermal growth factor receptor (EGFR) for which targeted agents are highly effective in causing tumors to shrink. However, it never cures patients and the tumor always grows back. This proposal focuses on why the cancer is not completely killed even though all of the tumor cells have this mutation, and how to overcome this problem and kill the cancer more thoroughly. Our published and preliminary data have demonstrated that targeted therapy rapidly induces drug persistent cancer stem cells (DPCs) within days of starting therapy, and these DPCs don’t die with the drug. We show that this therapy specifically activates other genes called Notch3 and β-catenin that are essential for this effect. We show in animal experiments that targeting both EGFR and β-catenin result in reduced numbers of DPCs, and improved depth and duration of response and overall survival. This is a completely different approach than trying to target drug “resistance” pathways that develop months after initiation of therapy due to the “persistence” of tumor in the early days of therapy. Our goal is to eliminate tumor persistence so that it doesn’t have the chance to develop resistance, resulting in the cure of these patients. In this application, we propose to study how this persistence happens and attempt to move toward curing these patients by targeting β-catenin in combination with EGFR in a pilot human clinical trial. Successful completion of the proposed research will increase our understanding of why tumor cells are not eradicated with EGFR targeted therapy and test a novel drug combination that we hope will improve the survival of these patients.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Only half of children with neuroblastoma that is found to be “high-risk” (HR-NB) live after getting the best known treatments. To change this, we need to know what makes HR-NB grow, and find new targets to attack. The New Approaches to Neuroblastoma Therapy (NANT) (www.nant.org) is a team of doctors working with patients and/or in labs to find new treatment ideas and test them in children whose tumor didn’t go away after getting the best known treatments. If NANT’s new treatments are safe and make some tumors get smaller, they are then tested in more children to see if the new treatment is better than the best-known treatments. A little blood, bone marrow, and tumor are also taken from patients on NANT treatments to study in labs to see why our new idea did or didn’t work, and how we can make them better. There are 18 NANT hospitals in the United States, Canada, Australia, and Europe. NANT is the only group working only on new/better HR-NB treatments. This grant will support NANT doctors, labs, and the people who work in the NANT office to quickly take new ideas from labs and turn them into treatments being given to children with HR-NB. It also helps us to store patient samples so they can be used to keep finding new and better ideas. Our goal is to find safe treatments that will help more children with HR-NB to live.
Funded in partnership with Cannonball Kids cancer Foundation, in memory of Tyler Trent
Glioblastoma (GBM) is the most aggressive and devastating brain tumor, and it currently has no known cure. Less than 20% of young adults diagnosed with GBM survive more than 24 months. GBM can resist treatment in many ways. These include expressing an enzyme called CD73 and changing the expression of proteins on its surface. Natural killer cells are able to fight and kill GBM, however this ability is often blocked around growing GBM cells. In order to rescue the activity of these cells, we are developing new immunotherapies by genetically modifying natural killer cells to shut down ways that GBM uses to grow. We are also combining these cells with drugs that can help them travel deeper into tumors. This immunotherapy is an entirely new way to treat GBM and has significant promise, for patients, over traditional treatments.
Funded in partnership with the Goldberg Family Foundation
We need better tools to screen for and diagnose cancer earlier and at a curable stage in individuals that carry inherited mutations such as BRCA1/2 and other cancer susceptibility genes that put them at highrisk for breast, ovarian, prostate, pancreatic and other cancers. We propose to use powerful new approachesfor “next-generation” DNA sequencing from standard blood samples to identify circulating tumor DNA mutations as a very sensitive markerof early cancers in high-risk individuals. These “liquid biopsies” may prove to be a far easier and more sensitive way to screen for cancer than our current imaging based approachesusing mammograms, MRI’s, etc. To this end, we have been collecting blood samples from our genetically high-risk patients with and without cancer, and before and after prophylactic or cancer surgeries, for liquid-biopsy analyses using technology developed at Stanford.
In 2018, 81,000 people were diagnosed with bladder cancer (BC) in the US and 17,000 people died from this disease. Three of every four new cases have an early stage of disease, called non-muscle invasive bladder cancer. This type of BC is treatable, but for over half of these patients the cancer keeps coming back and so these ‘high-risk’ patients need additional treatments. Today, we do not know which patients will have their cancer return and so we need to develop a way to know in order to help them sooner. Several cancer causing chemicals are associated with BC and so to help reduce new BC cases we need to identify and remove these chemicals from our environment. A new approach is necessary to tackle BC and our group has shown that our pet dogs can help. Each year in the US, over 60,000 dogs are diagnosed with BC. In this study, our team at NCSU College of Veterinary Medicine and Duke Cancer Institute will look for shared genetic changes in canine and human BC that may provide clues to why these cancers keep returning and how to prevent them. Our dogs live with us and so we will also study whether dogs with early BC share common chemical exposures in the home. This study of canine and human BC will allow us to determine how much help our pet dogs can provide us in looking for new ways to improve BC treatment for both ourselves and for them.
African Americans have the highest percentage of new cancer cases in the United States and the worst outcomes. Other diverse populations have difficulty getting to a cancer treatment center or need help figuring out the system one they arrive. 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. WFBCCC wants to make sure that everyone has access to the best cancer care possible. This may include patients participating in research that may improve outcomes for them but also may help provide information that can help tailor treatments for the next generation of cancer patients. It is important to make sure all populations are represented in studies that look at new treatments or supports for cancer patients. To meet that goal, we created a population health navigator program- people who are 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 is diagnosed with cancer, the navigator will assist that person by helping to remove barriers to care and will talk with patients about clinical research as part of their care.
Approximately 80,000 Americans will be diagnosed with bladder cancer in 2019 and 18,000 will die from their disease this year. Recent studies show that bladder cancer cells often carry a high number of genetic mutations which correlate with anti-tumor immune responses. New drugs known as immune checkpoint inhibitors (ICI), have produce dramatic clinical responses in up to 25% of bladder cancer patients, by enhancing anti-tumor immune responses that help control the tumor. However, despite intense efforts, biomarkers that predict response to ICI remain elusive. Furthermore, the mechanisms responsible for resistance to ICI are unknown. Predicting which patients respond to ICI would enable responders to be streamlined to receive ICIs, and resistant patients to receive alternative or combination therapies to improve their outcome. Pet dogs also develop bladder cancer that shares similar clinical, biological and genetic features with human bladder cancer. Despite standard of care treatment, most dogs will die of their disease within one year of diagnosis. Here we will investigate the genetic mutational burden in canine bladder cancer and determine whether it also correlates with tumor immune profiles. We will develop a canine ICI that can be used therapeutically in dogs with bladder cancer and we will determine whether effective ICI therapy is associated with enhanced anti-tumor immune responses and which factors or combination of factors predict ICI response. This work aims to establish the dog as a valuable model for human bladder cancer, provide a novel treatment for these dogs and guide biomarker discovery for humans.
Immunotherapy is a new treatment that uses certain parts of a person’s immune system to fight cancer. It is now used in combination with chemotherapy to treat a specific group of women with triple negative breast cancer who have disease that has spread to multiple parts of their bodies and who are not candidates for surgery.
Very few African American women were enrolled on clinical trials of immunotherapy. Therefore, we do not know if immunotherapy will have the same results in African American women as it does in Caucasian women.
The aim of our study is to increase awareness and education in African American women on the use of immunotherapy in breast cancer and to increase enrollment of African American women in a specific clinical trial which will open at the Winship Cancer Institute and Grady Memorial Hospital studying the combination of radiation and immunotherapy in women with triple negative breast cancer. We will accomplish this through a social media campaign on Facebook, Twitter and Instagram, patient educational pamphlets throughout Winship Cancer Institute and Grady Memorial Hospital and the support of an African American clinical research coordinator.
Through our program, we hope to increase the enrollment of African American women onto our immunotherapy clinical trial and answer important questions about the use of immunotherapy in African American women. If successful, the content we develop will set the stage for other educational material aimed at increasing African Americans enrollment on trials of immunotherapy regardless of disease site.
Peritoneal carcinomatosis (PC) — an aggressive metastasis of gastric cancer — is always fatal.
Approximately 20 percent of patients newly diagnosed with gastric cancer already have PC; and about 45 percent of those diagnosed will eventually develop PC. Researchers have a poor understanding of gastric cancer cells that populate the peritoneal cavity. Current therapies offer little help and research is limited. The lack of understanding of PC puts clinicians at a disadvantage when determining the best strategies for patients with this disease.
Researchers at The University of Texas MD Anderson Cancer Center are overcoming these obstacles through the Intraperitoneal Program. This program, which is led by Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology at MD Anderson, is aiming to conduct high-quality multiplex profiling of PC cells and stroma (surrounding tissue). The program allows Dr. Ajani and his team to generate multiplex data for a large number of samples from patients and use innovative tools that, he believes, will result in transformative ways this disease is treated.
To carry out this research, Dr. Ajani’s team has already collected abdominal fluid from many patients with intraperitoneal metastases. From these samples, they have identified cancer stem cells, which they believe are responsible for spreading into the peritoneal cavity. Eventually, Dr. Ajani’s team aims to develop a deeper understanding of the immune biology of the peritoneal cavity and how cancer stem cells recruit normal cells to be protected from the immune system.
Too many lives have been lost to this cancer. In order to develop therapies that can be tested in preclinical models, researchers need to conduct a deep dive investigation into PC using multidimensional integrative analyses to comprehensively profile the tumor and its microenvironment. The goal of this work is to discover therapeutic targets, biomarkers and signatures with prognostic and predictive potentials, enabling us to build illuminating predictive models. The researchers’ ultimate mission is to use every resource available to find viable therapies to fight this terrible disease.
The healthcare landscape has dramatically changed in South Florida, and we welcome you to be a partner in this transformation. Miami Cancer Institute at Baptist Health South Florida opened its doors in 2016 and is now seeing nearly 1,200 patients per day. The Institute, supported by a clinical and research alliance with Memorial Sloan Kettering, one of the leading academic cancer centers in the world, grants our patients access to the most advanced clinical trials for breast cancer. Patient accrual remains a huge challenge in clinical research, and the grant will go towards supporting recruitment for the important studies which in many cases, may give patients access to new therapies that are not yet readily available. The Institute will be proactive with the creation of recruitment materials as part of a well-coordinated campaign to address all aspects of enrollment as well as presenting information in an easy to understand and honest way including translation of all materials into Spanish. It is our goal to track enrollment efforts and adjust accordingly to what works best for our patient base and the community we serve. The mission of the breast clinical trial enrollment program is to provide innovative, patient centered cancer care through access to cutting edge treatments.
