Fewer than 5% of adult cancer patients in the United States are enrolled in clinical trials. In addition, minorities constitute a small proportion of individuals participating in cancer studies. These strikingly low figures delay scientific advances, limit generalizability of trial results, and limit patient access to cutting-edge therapies. Proposed reasons for low accrual include lack of study availability, stringent eligibility criteria, physicians’ biases and lack of awareness, logistical issues, and patient mistrust.
Parkland Health and Hospital System (PHHS) serves as the safety-net hospital for Dallas County. Parkland, in partnership with the University of Texas Southwestern, provides medical care to a large population that disproportionately includes underserved minorities. Cancer patients presenting to Parkland are typically diagnosed at a more advanced stage and are more likely to have had delays in their care.
Based on our previous observations, we believe that the greatest potential impact lies in addressing specific and modifiable aspects of patient care. We therefore propose a Breast Cancer Clinical Research Navigator with a role distinct from research coordinators that will focus on early identification of trial candidates, expediting initial patient evaluation, and improving provider awareness of trial options.
We believe that engaging a Breast Cancer Clinical Research Navigator in the ways outlined above, will result in early and integrated consideration and presentation of trial options and will impact both patient and clinician interest in clinical trials, thereby augmenting accrual.
Recipient of the V Scholar PLUS Award, a third year of grant support for V Scholars who have made exceptional progress in year 1 and 2 of their original grant
The precision oncology approach to the treatment of cancer bases treatment decisions on the biology of an individual’s cancer, most often using genetic alterations or mutations to inform therapy. This approach has been successful in a few cancer types, including lung cancer, melanoma, and chronic myelogenous leukemia where oral targeted therapies have led to both improved patient outcomes and fewer side effects compared to standard chemotherapy. However, this approach has not yet realized its full potential in these or other cancer types. In this proposal we plan to study new cancer-causing gene mutations involving the NTRK1, NTRK2 and NTRK3 genes, which are found in numerous types of cancer. We have already demonstrated that tumor cells treated with targeted therapies against this gene family can kill cancer cells in the laboratory. We have also observed early and dramatic tumor shrinkage in patients with different tumor types that share mutations in these NTRK genes. This proposal will focus on determining additional mutations of NTRK genes that may respond to therapy. The proposal will also study how cancer cells become resistant to targeted therapies and develop new laboratory models of NTRK+ cancer to develop new therapies for these cancers.
The promise of cancer therapies that target the mutationally activated “drivers” of malignant behavior is that highly selective drugs can be developed that will be effective with minimal side effects. However, that promise has not been achieved because most cancers rapidly develop resistance to these targeted therapies. Recent experience with the leukemias and lymphomas that respond to the drug ibrutinib provide a sobering example of both the successes and disappointments of these targeted approaches. Whereas many patients with malignancies of B-cells (Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma (MCL) or Diffuse Large B-Cell Lymphoma (DLBCL)) show a beneficial response to treatment with ibrutinib, the responses are generally incomplete and often are not durable. The goal of the collaborative research proposal from UVA and VCU is to elucidate the important mechanisms of intrinsic and adaptive resistance to therapies for B-cell malignancies, and use this understanding to develop RATIONAL combinations of drugs that target both the driver of malignancy and the resistance mechanisms. The two groups have over the past few years taken complementary approaches to tackling this problem, and some of these discoveries are now entering clinical trial. The UVA and VCU groups will utilize materials from these clinical trials, as well as preclinical models and patient samples to develop tools to match patients with the most appropriate drug combinations, and to develop additional combinations of targeted therapies that will have deeper and more long-lasting benefits.
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.
Ovarian cancer is the 5th cause of cancer death in women. Older women with ovarian cancer have a markedly worse survival rate than for younger ones. This is likely due to a combination of biology and a treatment-related factors. In this project, we will study these older women using a two-pronged approach. First, we will look at gene array data and assess which gene expression patterns correlate with a more aggressive behavior in older women, how they are modified by chemotherapy, and whether a targeted therapy can help control these deleterious patterns. Secondly, we will investigate ways to improve the delivery of chemotherapy by factoring in body composition and the functional impact of side effects. We will proceed in three steps. In step 1, we will use the Total Cancer Care (TCC) database, which combines gene arrays and clinical data to identify promising patterns to be focused on. In step 2, we will conduct a prospective study and collect samples after preoperative chemotherapy, to see which genes fail to be inactivated by chemotherapy, and how body composition is related to the blood levels of chemotherapy. In Step 3, we will add a targeted drug therapy to the standard chemotherapy for ovarian cancer to try to thwart the resistance mechanisms we identified and improve response. In one of the arms, the chemotherapy will be adapted to body composition and functional impact of side effects. To have enough patients, Steps 2 and 3 will be multicentric studies conducted within the Moffitt Oncology Network and Total Cancer Care Partnership.
2015 V Foundation Wine Celebration Vintner Grant in Honor of Rick and Elaine Jones With Support From Becky and Howard Young
Pancreatic cancer is an almost universally deadly disease because it spreads quickly to other organs (metastasizes) easily and there is no early detection mechanism. Surgery can be an effective treatment, but less than 10% of patients are diagnosed at a resectable stage. About 30% of patients with pancreatic cancer have locally advanced pancreatic cancer, where the cancer has not yet metastasized, but cannot be removed by surgery. The only way to kill locally advanced pancreatic cancer is with chemotherapy and radiation. Radiation therapy can kill any tumor but its therapeutic effects are limited by unavoidable damage to normal tissue near the cancerous target. For instance, adenocarcinomas of the pancreatic head require high doses of radiation to achieve tumor control, but these cannot be safely given to patient because the pancreas sits near a part of the small bowel called the duodenum, which is very sensitive to radiation damage. Thus, we can never give the amount of radiation needed to kill the tumor without causing undue harm to the duodenum (and the patient). My research will solve this problem by strengthening the duodenum and nearby tissues to withstand higher doses of radiation by activating the hypoxia-inducible factors (HIFs), which promote recovery from radiation treatments without protecting tumors. My published work has shown that HIF2 can reduce GI toxicity from radiation, and this proposal seeks to use this biology to make the duodenum more resistant to radiation toxicity to allow us to give higher doses of therapeutic radiation to the pancreatic tumors.
The purpose of our study is to test psychosocial interventions to improve quality of life (QOL) (psychological, physical, social and spiritual well-being) for Latinas with breast cancer and their family members or friends who are helping them during their cancer journey. Latinas and their family members/friends often experience severe psychological distress during cancer treatment and this distress can negatively affect health and well-being. Participants in our study are assigned to either an 8-week supportive health education intervention or an 8-week telephone interpersonal counseling intervention. Both the health education and the counseling is provided over the telephone, and each person who participates in the study is called separately. Our trained health care workers call the women and their family members/friends at times that are convenient for them. Sessions are about 30 minutes on the phone each week for 8 weeks. Using the telephone to deliver this service removes many of the access barriers normally associated with counseling or health education. Participants can receive help in the privacy of their own homes over the telephone. In addition to participating in the 8 education or counseling sessions, we ask the women and their family members/friends to complete some questionnaires 4 times over the next 6 months to determine if the intervention was helpful to them. All study related materials, assessments and sessions are conducted in English or Spanish, depending on the person’s preference. At the end of our study, we also tell them about any other clinical trials that may be of interest.
Lung cancer is the top cancer killer in the United States and worldwide, claiming over 1.5 million lives in 2012, according to the World Health Organization. The purpose of our research project is to understand how patients’ genetic ancestry contributes to the likelihood of acquiring specific harmful changes in DNA (“mutations”) in lung cells that lead to lung cancer. Mutations in the EGFR gene are important because EGFR mutations often cause lung cancer, especially in non-smokers. Significantly, patients whose lung cancers have EGFR mutations benefit from drugs targeting mutant EGFR, including gefitinib, erlotinib, and afatinib. Mutations in EGFR occur more frequently in lung cancer patients of East Asian or Latin American origin but the basis for this observation is a mystery, especially because these mutations are not inherited but arise after birth. Here, we propose to analyze DNA from 1500 Latin American lung cancer patients, to understand whether and how their genetic makeup leads to increased risk of developing EGFR-mutant lung cancer.
By defining the basis of increased risk of EGFR mutant lung cancer in Latin American populations, we could enable the use of effective existing treatments in this population. Additionally, if we can find a genetic marker for susceptibility to EGFR mutation, we could facilitate the screening, early detection and early EGFR-targeted therapy of lung cancer in at-risk populations. We therefore believe that our research plan could lead not only to an improved intellectual understanding of lung cancer but to improved outcomes for lung cancer patients from susceptible populations.
Mutations in the KRAS gene are one of the most frequent genetic alterations found in lung cancer, a disease that is associated with the highest cancer-related morality rate in the US. Despite their prevalence, we still do not have an effective therapeutic intervention to target lung cancers harboring KRAS mutations. In this application we will investigate novel approaches to inhibit the function of this protein in patient-derived (or ‘avatar’) models of lung cancer and then translate the most promising findings to early phase clinical trials.
Pancreatic cancer is a devastating disease. Current therapies for pancreatic cancer have modest effects as the 5-year overall survival is a discouraging 5-6%. One contributing factor to increased morbidity and mortality is cancer cachexia. Cachexia is defined as weight loss, muscle atrophy, fatigue, and weakness, in someone who is not actively trying to lose weight. Cachexia is a devastating condition affecting most cancer patients, but significantly more pronounced in patients with pancreatic cancer and is a significant therapeutic and personal dilemma. I have a significant background in clinical oncology with specialization in pancreatic cancer. The aims of my therapies are to improve and extend my patient’s quality of life. Unfortunately, our therapies can be premature or delayed primarily by the overall health of my patients. Premature in that we treat weak and malnourished patients that should not be given aggressive therapies for the risk of causing more harm than good. Delayed in that the patient is too weak and malnourished to receive any therapy and therefore will succumb earlier to their disease. With the expertise and passion of our collaborative group, we will investigate the possible biologic factors that contribute to pancreatic cancer cachexia. Our plan will be the future development of strategies to interfere with its deleterious effects on our patient population. In summary, we hope to improve the quantity of quality life in patients with pancreatic cancer.
Mailing List
