Dr. James M. Ford, M.D., is an Associate Professor of Medicine, Pediatrics and Genetics at Stanford University School of Medicine. He is the Director of the Stanford Cancer Genetics Clinic and the Stanford Clinical Cancer Genomics Program. A recipient of The V Foundation Translational Research grant in 2002, Ford joined the Scientific Advisory Committee in 2003.
Dr. Ford’s research goals are to understand the role of genetic changes in cancer genes in the risk and development of common cancers. He studies the role of the p53 and BRCA1 tumor suppressor genes in DNA repair, and uses techniques for high-throughput genomic analyses of cancer to identify molecular signatures for targeted therapies. Dr. Ford’s clinical interests include the diagnosis and treatment of patients with a hereditary pre-disposition to cancer. He runs the Stanford Cancer Genetics Clinic, that sees patients for genetic counseling and testing of hereditary cancer syndromes, and enters patients on clinical research protocols for prevention and early diagnosis of cancer in high-risk individuals.
Ford graduated Magna Cum Laude with a B.A. degree from Yale University in 1984 and earned his M.D. degree from Yale in 1989. He has been at Stanford ever since, serving as an intern, resident and fellow before earning his postdoc and becoming Assistant Professor in 1998.
More children die from brain tumors than any other type of cancer, and the most common type of brain tumor in children is medulloblastoma. Children with medulloblastoma are treated with surgery, radiation, and chemotherapy, and more than 50% of patients survive into adulthood. However, the treatments used for medulloblastoma lead to many long-term side effects, including growth defects, hormone abnormalities, and impaired intelligence. Like all cancers, medulloblastoma is caused by uncontrolled cell growth. Approximately one-third of medulloblastoma cancers arise when a particular signal that tells brain cells to grow, called Hedgehog, gets stuck in the “on” position. We are interested in uncovering exactly how Hedgehog signals tell medulloblastoma cells to grow. To do so, we are investigating how the Hedgehog pathway is activated, and how Hedgehog activation regulates the expression of other signals to influence cell growth. In particular, we are using existing drugs to understand whether block critical mediators of Hedgehog effects blocks the growth of medulloblastoma. Understanding how Hedgehog signals cause cancer may show us how to turn off these signals, and potentially, lead to new therapies for medulloblastoma.
Funded by the 2015 Wine Celebration Fund a Need, including donations raised by the Dick Vitale Gala and Bristol-Myers Squibb
Recent research revealed that malignant gliomas in children often have common gene mutations in a molecule named H3.3, which is a component of the human genome. Approximately 30% of pediatric glioblastoma and 70% of diffuse intrinsic pontine glioma (DIPG) cases have the same mutation which causes a change in the H3.3 protein. The human immune system, such as T-lymphocytes (T-cells hereafter), do not normally react to normal proteins, but can recognize and attack cells that have abnormal proteins. Therefore, cancer-specific mutations can be suitable targets for cancer immunotherapy, such as cancer vaccines and adoptive T-cell transfer therapy (i.e., infusion of large number of T-cells). Indeed, immunotherapy using patients’ own T-cells that are engineered to recognize cancer cells have shown remarkable success in other cancers, such as acute lymphocytic leukemia in children. However, it is also important to ensure that those T-cells attack tumor cells but not normal cells. We recently found that the common mutation in H3.3 includes cytotoxic T cells which can kill glioma cells that have the mutation but not cells without the mutation. We are proposing two lines of translational studies. First, we will isolate genes for the T cell receptor which allows the specific recognition of mutated glioma cells. This will lead to a near future development of adoptive transfer immunotherapy. Concurrently, we will design and conduct a pilot vaccine trial using synthetic peptide for the mutated part of H3.3 in children with H3.3-mutated DIPG or high-grade glioma.
Funded by the Dick Vitale Gala in memory of Lauren Hill
We have recently demonstrated that neuronal activity in the cerebral cortex can drive the growth of deadly brain tumors called high-grade gliomas. High-grade gliomas include tumors that affect children, teens and adults, such as glioblastoma, anaplastic oligodendroglioma and the childhood tumor diffuse intrinsic pontine glioma (DIPG). High-grade gliomas are the most lethal of all brain tumors. An important way that brain activity promotes the growth of these brain tumors is through release of a molecule called “neuroligin-3”. The purpose of this project is to develop a new therapy for these deadly brain cancers designed to sequester neuroligin-3 like a molecular sponge. We have shown that such a strategy is effective in principle, and now seek to test and optimize this strategy in preclinical models of high-grade glioma.
Neuroblastoma is the most common extracranial solid tumor of childhood. Amplification of the MYCN proto-oncogene occurs commonly in high-risk neuroblastoma and marks a particularly aggressive and lethal form of the disease. We and others have described an array of highly targeted inhibitors to block kinases both upstream and downstream of MYCN in neuroblastoma. Among these targeted inhibitors, we have recently described a novel conformation disrupting inhibitor of Aurora Kinase A which potently induces MYCN degradation through an allosteric change in Aurora Kinase A. Because these inhibitors target distinct members of the MYCN pathway, we hypothesize that they will have nonoverlapping toxicities and that combinations of MYCN targeted therapies will more potently block MYCN. In Aim 1 of this proposal we will rigorously test combinations of MYCN targeted therapies for pre-clinical efficacy with the goal of rapidly translating combinations into patients with neuroblastoma. In Aim 2 of this proposal we will develop our novel conformation disrupting Aurora Kinase inhibitor to “dial out” toxic Aurora Kinase A activity and finesse more potent MYCN degradation in neuroblastoma to optimize therapeutic efficacy. Successful completion of this proposal will result in direct and rapid translation of therapeutic combinations of MYCN targeted therapies into children with neuroblastoma and provide new clinical grade drug candidates for conformation disrupting Aurora Kinase A inhibitors.
Lung cancer is the most common cause of cancer death in the US and worldwide. Because it has a five-year survival rate of only 18 percent, new therapeutic approaches are urgently needed. We propose to develop novel therapies by targeting the Wnt signaling pathway, which is involved in normal cell growth, but is also implicated in lung cancer development, progression and metastasis. Historically, Wnt signaling has been challenging to target directly, but epigenetic changes that chemically modify DNA or DNA packaging proteins, known as histones, can turn Wnt signaling on or off. In over 80% of lung cancers, the WIF1 protein that normally turns Wnt signaling off, is not produced. We showed that a drug which alters specific modifications to histone 3 restores the production of WIF1, shuts down Wnt expression and induces lung cancer cell death. To advance our observations from bench to bedside, we will 1) determine how specific histone modifications and changes to WIF1 production and Wnt signaling correlate with the disease and its clinical outcomes; 2) analyze the biochemical mechanisms that alter histone modifications to suppress Wnt signaling; and 3) test the effectiveness of two experimental drugs that alter histone modifications to inhibit the tumorigenesis and progression of human lung cancer transplants in mouse models. Successful completion of these studies are expected to unravel important epigenetic pathways that promote Wnt signaling to induce lung cancer, and to identify new drug targets that will suppress Wnt signaling and dramatically improve the outcomes for lung cancer patients.
USC Norris Comprehensive Cancer Center offers over 23 trials for patients with breast cancer at the USC Norris Cancer Hospital and at the Los Angeles County (LAC) USC Medical Center, making them accessible to all. Participation in cancer clinical trials is a key measure for delivery of quality cancer care. Adult participation in cancer clinical trials remains at 3% and participation among ethnic and racial minorities and medically underserved communities is even lower. The Clinical Investigation Support Office, led by Dr. Anthony El-Khoueiry is dedicated to increasing minority accruals to clinical trials and has enlisted support from Dr. Julie Lang, a breast surgeon to support patient education and enrollment efforts. We plan to leverage our strong tradition of minority accrual (minority patients represent 56% of accrual to interventional therapeutic trials at USC Norris) and further enhance access to clinical trials for minority patients.
