From Patient to Healthcare Hero: Carey is Riding for Research
Read moreType: Game-Changer
Gregory Smith, M.D.
Funded by The V Foundation Wine Celebration
Shakeel Modak, M.D. & Brian Kushner, M.D.
Funded by the Dick Vitale Gala in memory of Eddie Livingston
Anti-GD2 monoclonal antibodies are now standard of care for patients with high-risk neuroblastoma, but there is little information on their biodistribution and tumor targeting in patients. We are developing a third generation anti-GD2 MoAb humanized 3F8 (hu3F8) for therapy of neuroblastoma. This proposed study will use a small dose of radioactive hu3F8 to determine its distribution and targeting using PET imaging which can provide sophisticated and quantitative data. This information will be critical in refining current dosing regimens for hu3F8 and improve the design of future clinical studies. Moreover, if specific tumor targeting can be demonstrated, as study of radioactive hu3F8 for therapy of patients with poor-prognosis neuroblastoma will be initiated.
Victor van Berkel, M.D., Ph.D.
Funded by the Louisville Friends of V
Lung cancer is responsible for more cancer deaths each year than breast, colon, and prostate cancer combined. Part of the problem resides in the lack of symptoms associated with lung cancer – many patients already have advanced disease on presentation. Currently, the best method for identifying lung cancer involves computed tomography (CT scans) of the chest; while this has been demonstrated to improve cancer mortality by identifying earlier stage cancers, it also identifies multiple nodules within the lungs that are not malignant. In an effort to more precisely diagnose early stage lung cancer in at risk individuals, our group has turned to breath analysis. Human breath contains thousands of compounds from atomic hydrogen to complex biological molecules. Recently a class of organic compounds known as carbonyls have been associated with lung cancer. Our research group has devised a simple method to extract and measure these compounds from a single breath. We have identified four specific cancer markers among these compounds – the chance of having cancer increases with the number of elevated cancer markers identified in the patient’s breath. The proposed project seeks to determine if breath analysis is as effective as CT scan in screening for lung cancer by comparing the two methods in the same patients. We will also study patients after a cancer has been resected to determine if recurrence of cancer can be effectively detected by breath analysis relative to CT scanning.
Clare Yu, Ph.D. & Juliana “Julie” Wortman
Funded in Collaboration with Stand Up To Cancer (SU2C)
The goal of an exciting new form of immunotherapy is to get the immune system to kill cancer cells. When killer T cells arrive to kill tumor cells, some cancer cells are able to prevent this attack by inserting a protein that acts like a “key” (e.g., a PD1 ligand where ‘PD’ stands for Programmed Death) into a “keyhole” (e.g., a PD1 receptor) on the killer T cell. Anti-PD1 immunotherapy drugs like nivolumab and pembrolizumab block the keyholes and prevent cancer cells from turning off the killer T cells. Such immunotherapy drugs are particularly effective when killer T cells have infiltrated the tumor. The goal of our project is to understand what features of the microenvironment of the tumor enhance the infiltration of killer T cells into the tumor. The tumor microenvironment, which includes cells, protein structures (like collagen fibers) made by some of these cells, blood vessels, and lymph vessels, typically provides a supporting environment for the tumor to grow. However, changes to the tumor microenvironment can inhibit the growth of the tumor and even lead to its demise. We will carefully characterize the spatial arrangements of the different types of cells and structures in the breast cancer tumor microenvironment in an effort to determine what enhances infiltration by killer T cells. Knowing this could lead to more effective immunotherapy.
Herbert Levine, Ph.D. & Xuefei Li, Ph.D.
Funded in Collaboration with Stand Up To Cancer (SU2C)
Clinical oncology has entered an era of personalized molecular diagnosis and targeted therapy. This means treatments are tailored to each patient based her tumor’s histopathological and genetic characteristics. Such personalized treatment often involves a combination of multiple active agents to treat one tumor. In estrogen receptor positive (ER+) breast cancers, the three most promising classes of treatments are hormonal therapy, PI3K pathway inhibitors and cell cycle inhibitors.
Although patients derive benefit from such treatment, for most of the advanced ER+ breast cancers, the tumors respond initially but then stop responding, which is called “resistance” to therapy. Unfortunately, this resistance results in death in most cases of advanced breast cancer. Treating these cases requires developing novel therapeutic strategies to overcome the resistance based on an understanding of the mechanisms of resistance.
In this project, we leverage the leading edge technology of high-throughput whole-genome screening to discover mechanisms of resistance to each of three classes of drugs and all of their combinations. We also characterize the identified genes and their function in a variety of breast cancer cell types and mouse models. The knowledge of resistance to treatment obtained through this project will guide our effort to design more effective combinational therapeutics to overcome resistance. Ultimately, this work will be translated to benefit most of the patients with ER+ breast cancers.
Steven Altschuler, Ph.D. & Xiaoxiao Sun, Ph.D.
Funded in Collaboration With Stand Up To Cancer (SU2C)
One of the foremost challenges to cancer treatment is the emergence of drug resistance. Adding complexity to this problem is the realization that both the initial as well as the emergent drug-resistant cancer population can be in highly heterogeneous epigenetic and genetic states and from populations of very different sizes. This heterogeneity makes it difficult to predict which cells will survive drug treatment and which drug-resistance mechanism will emerge, repopulate the cancer cell population and ultimately cause relapse. Our goal is to better understand which cellular subpopulations are predisposed to initially survive targeted therapy, how diverse these subpopulations are from one another, and combination therapies would best target these subpopulations. To accomplish this, we will make use of novel high-throughput assays for drug treatment, genomic and image analysis and mathematical analysis of cellular heterogenity and evolution. These studies will address questions that are central to the fields of cancer biology, modeling, and cancer therapeutics, and allow us to test novel therapeutic approaches that can then be rapidly translated to the clinical context.
Walter Stadler, Ph.D.
Funded by the Windy City Golf Classic
In memory of Michael Klein
UCSF Helen Diller Family Comprehensive Cancer Center
