The V Foundation for Cancer Research Expands Executive Leadership Team
Read moreState: North Carolina
Ian J. Davis, M.D., Ph.D.
Abeloff V Scholar*
Gang (Greg) Wang, Ph.D.
Abeloff V Scholar*
Enzymes that modify chromatin (the physiological form of DNA) are often found abnormally expressed, mutated, and/or hyper-activated among various forms of blood malignancies. Somatic mutations of EZH2, a gene that encodes a critical chromatin-modulating enzyme, are responsible for over 10-20% of clinically diagnosed diffused large B-cell lymphomas and follicular lymphoma. These mutations are known to lead to EZH2 hyperactivity in cancer cells. However, it is largely unclear how EZH2 is associated with chromatin, which is critical for EZH2’s role in gene control and cancer promotion. Using the biochemical approach as a discovery tool, we demonstrate that the activities of EZH2 rely on a critical interacting factor PHF19 or PHF1, which opens a possibility for pharmacological manipulation and makes them ideal drug targets. Abnormalities of both PHF1 and PHF19 have been frequently found in human cancers including lymphoma patients, which resonate well with their roles in regulating EZH2 during cancer development. Future investigation shall be performed to design new ways for targeting EZH2’s cofactors as novel anti-cancer interventions.
Kris C. Wood, Ph.D.
2013 V Foundation Wine Celebration
Volunteer Grant in Honor of
John and Anne Sachs
Michael J. Emanuele, Ph.D.
Chad V. Pecot, M.D.
Cancer is a leading cause of death in the U.S. and the world, largely due to our inability to block the spread of disease (termed metastases). However, over the past several years the roles of recently discovered genes, called microRNAs, have been shown to play vital roles in controlling cancer growth and metastases. One group of these microRNAs, called the miR-200 family, has shown particular promise by blocking many critical functions known to drive cancer. Recently, we discovered that the miR-200 family could block the formation of new blood vessels inside tumors, which resulted in decreased metastases. Our proposal focuses on understanding how miR-200 blocks formation of blood vessels in cancer, and further explores the use of miR-200 delivery as a new therapeutic option to treat cancer.
Peter S. Turk, M.D.
Funded by Papa John’s International, Inc.
Tian Zhang, M.D.
Funded by friends of TK and Virginia Wetherell
Metastatic castration resistant prostate cancer (mCRPC) – prostate cancer which is resistant to androgen deprivation therapy – can be often aggressive and lethal. The androgen receptor (AR) has an important role in the disease course of prostate cancer, since both enzalutamide and abiraterone acetate improve overall survival by exerting effects on the AR pathway. Our preclinical data shows that AR can increase proteins that are needed maintaining copper balance, such as the copper transporter protein, which we found in prostate cancer samples. To take advantage of the copper biology in prostate cancer, we performed a “conditional lethal” screen for drugs that exert their cancer-killing effects based on the presence of copper. This screen identified disulfiram “Antabuse”, as a potential drug for prostate cancer. Antabuse has been tested before in prostate cancer but never in the presence of copper. Mouse models of prostate cancer have shown that those cancer masses can shrink when Antabuse is given along with copper. Therefore, we propose to study the combination of Antabuse and intravenous copper, to find the safety profile for this combination of drugs. In addition, we will study the copper uptake of these patients’ prostate cancers using a radiolabeled copper PET scan. These studies will allow us to see whether the baseline copper uptake of a patient’s prostate cancer is linked to their response on the combination of Antabuse and intravenous copper.
Charles Perou, Ph.D.
Funded in honor of Nick Valvano by a challenge grant with
The University of North Carolina at Chapel Hill.
Personalized medicine for cancer patients is a current goal of biomedical research. A few gene expression-based assays have already proven to have clinical utility (i.e. value), especially for breast cancer patients (see 2016 ASCO biomarker guidelines). Therefore the continued discovery and clinical development of additional gene expression assays could be an important aspect for furthering personalized treatments. Here we propose to develop a new generation of gene expression-based assays for possible use in cancer care. The goal of this proposal is to further develop and test a genome-wide RNA-sequencing assay and it’s companion bioinformatics tool, for the automated classification of a tumor according to 300 different expression signatures. These signatures span a broad range of biological phenotypes including the microenvironment (immune cells, fibroblasts), tumor features (growth factor signaling pathways), and of cancer stem cells. Some of these 300 signature may eventually be of clinical value, and so in this proposal we will create a new technological platform with linked bioinformatics, to provide these signatures as new potential biomarkers for future clinical testing.
Chad Pecot, M.D.
Funded in partnership with
the Lung Cancer Initiative of North Carolina
utilizing Stuart Scott Memorial Cancer Fund matching funds
While newer treatments for some types of lung cancers have improved patient survival, similar advances in squamous cancers of the lung, head and neck have been slow. Recent studies of the genes that characterize squamous cancers have revealed they are very complicated with no clear “smoking gun” way of attacking them. However the use of new therapies that activate the immune system has demonstrated exciting promise in squamous cancers.
We have found a new class of squamous cancers whose tumors take advantage of the immune system. We have created a list of genes that identifies patients with these types of cancers. This is the basis for a clinical trial we are developing. However, an important unmet need in North Carolina is an improved understanding of squamous cancers in black patients.
We believe that our list of genes will help determine whether black patients will benefit from immune therapies. We also believe that the amount of CD14 protein in their tumors, which is found on certain immune cells, will be helpful for a clinical trial we are creating. Building off of ongoing and upcoming clinical trials, the objectives of this proposal are to determine in black patients with squamous cancers whether our gene signature predicts for benefit to immune therapies already available to our patients. We also plan to find out whether the CD14 protein on these tumors will be useful for a clinical trial we are developing.
