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.
V Scholar Plus Award- extended funding for exceptional V Scholars
Myeloproliferative neoplasm (MPN) is a chronic blood cancer without curative treatments. In MPN, blood stem cells obtain mutations that result in excessive numbers of blood cells. Mutations in a gene named calreticulin have been recently found in a large percentage of MPN patients. It is unknown how calreticulin mutations drive MPN. Our goal is to identify how calreticulin mutations cause MPN and to develop drugs targeting calreticulin to treat this disease.
V Scholar Plus Award- extended funding for exceptional V Scholars
Aggressive lymphomas are cancers of white blood cells. The most common type is called diffuse large B cell lymphoma (DLBCL). Most patients with DLBCL can be cured by chemotherapy, but some patients either do not respond to treatment or the disease comes back after a certain time (‘relapse’). If we can identify those patients likely to relapse earlier, we hope to improve their chance of survival. Circulating tumor DNA (‘ctDNA’) is DNA that comes from tumor cells and gets in the blood stream. CtDNA in the patient’s blood can be analyzed to get more information about the tumor. In this study, we developed a blood test to profile ctDNA at different stages of the disease and to identify patients at risk for relapse. We found that ctDNA in the patient’s blood contains information that can be used to tell how well the patients will do with chemotherapy. We also observed that analysis of ctDNA over the course of treatment could show how their lymphomas change over time. For example, we detected new mistakes (‘mutations’) in ctDNA that could be used as an early signal to predict that certain treatments would no longer work in these patients. Also, we found that ctDNA in the blood after treatment predicts disease relapse months earlier than any other clinical method. Our test can also give physicians early warning that the tumor is changing from a slow growing to a fast growing lymphoma type. All this information in ctDNA can be used to learn more about lymphoma biology and to find patient groups with high risk for relapse.
Each year in the United States over 30,000 patients with breast cancer are treated with a class of drugs known as the anthracyclines. The anthracyclines are one of the oldest and most effective chemotherapies for breast and other cancers. However, some patients do not benefit from this therapy for reasons that are not understood. Moreover, because the anthracyclines target TopoII isomerase (TopoII), a remarkable protein that is vital for normal cellular functions such as untangling DNA, they can have serious side effects. Recently, we have found that we can predict whether cancer cells will respond to TopoII inhibitors based on their genomic profile. Our over-arching goal is to spare patients treatment with this highly toxic class of drugs if they will not benefit from their use. By performing a simple genomic test on the patient’s tumor sample obtained at the time of diagnosis, we aim to predict which patients will benefit from anthracyclines and thereby inform treatment decision-making. In this manner, treatments can be personalized so that patients receive the best possible current therapy to treat their specific tumor, while being spared ineffective drugs and their side-effects.
This research will help us improve a new type of therapy for children with neuroblastoma. Neuroblastoma is a deadly tumor in the nervous system outside the brain. With this therapy doctors administer both chemotherapy and a protein (antibody) that attaches to tumor cells at the same time. This combination, a form of chemo-immunotherapy, was tested on children whose tumors had not decreased even after many rounds of chemotherapy. These children would have died, but chemo-immunotherapy literally melted the tumors off after a few rounds of treatment. The results of this study have not been published yet but are already being used by doctors to successfully treat these children.
Despite this great outcome, half of the children did not respond to the new treatment. There is still a lot to learn about chemo-immunotherapy. In this study, we will test patients’ tumors and find out how their blood cells change with chemo-immunotherapy. We hypothesize that chemo-immunotherapy is assisted by white blood cells destroying tumor cells. Our goal is to study how tumor cells stop or slow down the effect of this therapy. If we are successful, we can modify chemo-immunotherapy to work in all children with neuroblastoma.
A set of proteins are highly active in cancer. They can add small groups to a series of target proteins. These uncommon additions are often linked with tumors found in breast, liver, and other tissues. To date, it is still unclear how those aberrant proteins cause cancer. To answer this question, it is crucial to know all the targets that they act on in live cancer cells. But no method has been made available to resolve this key issue. In this project we are aimed to create an innovative platform to achieve this goal. Our research plan will use chemistry and biotechnology to make new tools for target identification. A particular member in this group will be chosen for this work. Because it shows much higher activities in diverse types of cancer. The full range of targets for this protein in live cancer cells will be clearly assigned for each specific type of cells. Moreover, the patterns, levels, and time courses of such additions in live cells can be directly viewed and precisely measured by our creative approach. These findings will lead to unveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this work will advance our understanding of cancer. Importantly, it will foster the development of new approaches for cancer detection and treatment.
Prostate cancer is the second most frequently diagnosed cancer worldwide. In the US, more than 230,000 cases are diagnosed yearly, affecting 1 in 7 men. If detected early, the cure rate for these cancers is high – nearly all patients will be disease-free after five years. However, in patients whose cancers either re-appear after treatment or spread to other organs, therapies are limited mainly to symptomatic relief. Patients diagnosed at this stage usually live no longer than 20 months. Therefore, a major challenge in treating advanced prostate cancer is that the standard therapies, including radiation and medicine, are not effective in killing these cancer cells.
A small proportion of tumor cells, known as cancer stem cells (CSCs), is particularly important in promoting cancer, because they 1) can give rise to an entire tumor from a single cell, and 2) are more resistant to treatment than other tumor cells. Efforts to identify and then kill CSCs hold the key to effective prostate cancer treatment. The goal of our work is to define the molecular mechanisms that drive growth of prostate cancer CSCs. Once identified, those factors could serve as “biomarkers” or diagnostics. In addition, drugs could be designed to target those factors as a way of blocking tumor growth.
2016 V Foundation Wine Celebration Volunteer Grant
in honor of Pack and Susan and Sheryl Warfield
EBV infects over 90% of the population. It causes infectious mononucleosis (“mono”) among adolescents and 200,000 cancer cases worldwide every year. People infected by EBV may develop Burkitt lymphoma, a disfiguring disease common in children in Africa, Hodgkin lymphoma, head-and-neck cancer, and stomach cancer. EBV infection is typically mild but the virus remains in the body. It can become active again and cause disease in people with a weakened immune system, such as transplant or AIDS patients. Diagnosis and treatment of cancer related to EBV infection can be difficult. Even though we have known EBV causes cancer in humans since 1965, no vaccine exists. Scientists agree on the urgent need to develop one. Our goal is to develop a safe and effective vaccine to prevent and cure EBV-driven cancers. We will develop a vaccine using virus-like particles (VLPs). When a person receives the VLP-vaccine before EBV infection, the body will prepare itself to fight infections with antibodies. Also, immune cells will be ready to identify and kill cancer cells hiding EBV. We know our VLP-vaccine works in mice. We will repeat our work in an improved mouse model that has human immune cells. We predict that VLP-vaccine will cause antibodies to be made and will prepare immune cells to fight EBV infection and cancer cells. If successful, we will test the vaccine in healthy patients to prove its safety. Then, clinical trials in EBV-infected patients will test if the vaccine works, before it is used in the clinic.
Ovarian cancers are among the most deadly cancers for women. We need better drugs to treat women with ovarian cancer. Recent studies show that certain ovarian cancers have mutations in unique genes. For example, 60% of epithelial ovarian cancers (EOC) have mutations in the ARID1A gene. This is an important clue to understand EOC and how to treat it. ARID1A mutation forces these cancers to rely on the related protein ARID1B. ARID1B is thus an attractive target for drug discovery. ARID1A and ARID1B are proteins that control gene transcription. However, we do not why ARID1B is vital for ovarian cancers. Using new methods, we will find the genes that ARID1B controls in EOC. We will design a system to eliminate ARID1B in EOC to test if ARID1B is a good drug target. Cancers can often find ways to escape our drugs and come back. We will find loopholes that ovarian cancers use to escape ARID1B elimination. Our goal is to find new strategies to treat women with ARID1A mutant EOC.
Blood cancer affects thousands of individuals each year, and despite impressive early therapeutic advances, cure rates for most blood cancers have reached a plateau. Moreover, most therapies that are currently used do not specifically target blood cancer cells and therefore lead to undesirable side effects in a large number of patients. There is therefore an urgent need for developing safer new drugs for this devastating disease. The focus of this research proposal is to define the molecular mechanisms of a specific sub-type of acute myeloid leukemia that mostly affects children and young adults but is also seen in older patients. In this project, we will make use of molecular, genetic and biochemical methods to identify ways and means by which genes that are mis-regulated in these tumors lead to cancer development. Based on our preliminary findings, we propose that our approach may lead not only to a more detailed understanding of this specific sub-type of blood cancer, but also to novel treatment strategies.
