«FY 2010 House Appropriations Committee Report 111-220 and FY 2010 Senate Appropriations Committee Report 111 -66 T a b l e of Contents National ...»
SIGNIFICANT ITEMS (Sis)
FY 2010 House Appropriations Committee Report 111-220
FY 2010 Senate Appropriations Committee Report 111 -66
T a b l e of Contents
National Institutes of Health - Institutes and Centers
National Cancer Institute (NCI) 1
National Heart, Lung, and Blood Institute (NHLBI) 24
National Institute of Dental and Craniofacial Research (NIDCR) 42
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 45 National Institute of Neurological Disorders and Stroke (NINDS) 68 National Institute of Allergy and Infectious Diseases (NIAID) 83 National Institute of General Medical Sciences (NIGMS) 97 National Institute of Child Health and Human Development (NICHD) 98 National Eye Institute (NEI) 114 National Institute of Environmental Health Sciences (NIEHS) 119 National Institute on Aging (NIA) 123 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 132 National Institute on Deafness and Other Communication Disorders (NIDCD) 144 National Institute of Mental Health (NIMH) 156 National Institute on Drug Abuse (NIDA) 159 National Institute on Alcohol Abuse and Alcoholism (NIAAA) 172 National Institute of Nursing Research (NINR) 174 National Human Genome Research Institute (NHGRI) 176 National Institute for Biomedical Imaging and Bioengineering (NIBIB) 177 National Center for Research Resources (NCRR) 178 National Center for Complementary and Alternative Medicine (NCCAM) 184 National Center on Minority Health and Health Disparities (NCMHD) 185 Fogarty International Center (FIC) 193 National Library of Medicine (NLM) 199 Office of the Director (OD) 201 National Cancer Institute (NCI) House Significant Items Item Adult Acute Leukemia - The Committee is encouraged by ongoing research on adult acute leukemia particularly in understanding how changes in a person's DNA can cause bone marrow cells to develop into leukemia, the detection of minimal residual disease which can indicate a relapse in the disease, and the discovery of more effective chemotherapy drugs. The Committee encourages NCI to expand current studies and support promising new research through all available mechanisms. (p.108) Action taken or to be taken NCI is funding research on the epigenetic regulation of gene expression that may contribute to progression and survival in acute leukemia. Recent studies show that there may be a distinct type of acute leukemia associated with a profound epigenetic silencing (DNA methylation) of genes suppressing the expression of important developmentally related transcription factors (HOX genes). This type of acute leukemia may have a longer survival time and greater responsiveness to chemotherapy. In addition, NCI researchers are developing agents that target epigenetic mechanisms to treat acute myeloid leukemia (AML). An NCI team reported combining two inhibitors (3-Deazane-planocin A and panobinostat) might be an effective and selective epigenetic therapy for AML.
To identify DNA changes predictive of disease stage and progression in myelogeous leukemia and acute lymphocytic leukemia, NCI sponsored a high-resolution analysis of total gene expression. Important changes in the expression of the number of gene copies of specific genes and significant chromosomal abnormalities were detected in cells during disease progression. These striking genetic differences were detected in the progression of both lymphoid and myeloid leukemias to their most serious and dangerous stages.
These findings will assist in developing targeted therapies.
NCI is supporting a Specialized Program of Research Excellence (SPORE) that has been studying leukemia/bone marrow microenvironment interactions. The group previously reported that cells arising from bone marrow inhibit chemotherapy's ability to cause cell death in acute myeloid leukemia. A new study shows that targeting the bone marrow cells’ specific inhibitors makes leukemic cells more likely to be destroyed by chemotherapy.
In a collaborative effort, NCI investigators evaluated survival patterns of ~9,700 registered AML patients diagnosed in Sweden in 1973 to 2005 and found AML survival has improved during the last decades. However, the majority of AML patients die of their disease and age remains an important predictor of prognosis.
The NCI-sponsored Eastern Cooperative Oncology Group reported that higher dose daunorubicin as part of standard therapy for AML resulted in improved overall survival, compared to standard dose daunorubicin, with no increase in toxicity.
1 An important component for curative therapy in AML is allogeneic bone marrow transplantation. Since more than half of those who develop AML are generally deemed not eligible for transplant due to advanced age, the NCI-sponsored Cancer and Leukemia Group-B (CALGB) has explored the use of transplant for individuals with AML. The initial clinical trial results appear favorable. Efforts to improve this treatment modality in the older patient population with AML are ongoing.
An international collaboration led by the NCI-sponsored CALGB is focusing on a rare type of AML with extremely poor survival. This clinical trial utilizes a novel agent targeting a molecular defect (FLT3) and will determine if this approach improves the survival of these patients.
Item Blood Cancers- The Committee is aware that there are currently over 800,000 blood cancer patients living in the United States, and that the incidence of certain blood cancers has increased in recent decades. Public Law 107-172 directed NIH to expand, intensify, and coordinate programs for the conduct and support of research with respect to blood cancer, and particularly with respect to leukemia, lymphoma, and multiple myeloma. These diseases constitute one of the leading causes of cancer deaths. In addition, the Committee urges NCI to increase its focus on more rare forms of blood cancer such as Waldenstrom's macroglobulinemia. (p.108) Action taken or to be taken NCI is promoting research on the development and validation of biomarkers for the early detection, prediction, and recurrence of blood cancers, especially in high-risk individuals, as well as for risk assessment of primary and secondary hematopoietic malignancies. In addition, development and improvement of technologies and methods for quantitative detection of novel biomarkers is ongoing. An international effort lead by NCI is focused on identifying biomarkers, novel targets, and combination therapies for the development of early phase clinical trials for multiple myeloma (MM) patients.
Ongoing genome-wide association studies are examining the effects of common genetic variants in relation to non-Hodgkin lymphoma susceptibility and survival as well as key genes that may contribute to lymphomagenesis. NCI researchers are investigating the causes of blood cancers in the general population by large-scale epidemiological studies with biomarkers to uncover lifestyle and environmental risk factors, gene-environment interactions, the role of immunity and infection, and precursor lesions. In addition, NCI is actively recruiting new families to participate in its ongoing research investigating familial occurrences of blood cancers. The goal of these studies is to identify both genetic and environmental components of familial risk.
This year, NCI expanded the number of hematologic malignancy SPOREs by two:
leukemia and lymphoma. The existing SPOREs reported new advances in genomic characterization of hematologic diseases, the development of new treatment strategies, and insights in risk assessment. A novel, high-resolution genomic approach was used to better characterize the recurrent chromosome abnormalities associated with Waldenstrom's macroglobulinemia (WM) pathogenesis.
2 NCI has made significant efforts to expand and intensify treatment-changing clinical research in blood cancers, including rare conditions, in the past year. Current clinical trial efforts include three complimentary phase III studies in MM, a phase III trial in the rare and lethal blood cancer primary amyloidosis, several ongoing clinical trials enrolling patients with WM focused on specific pathways, and a new bone-marrow transplant protocol.
NCI investigators recently reported the following significant findings in blood cancer:
• Abnormal white blood cells can be present in patients' blood more than six years prior to the diagnosis of chronic lymphocytic leukemia;
• Sets of genes were identified in diffuse large B-cell lymphoma that influence the effectiveness of treatment and contribute to patient survival;
• Monoclonal gammopathy of undetermined significance was shown to precede MM;
• Several studies reported the impact of gene deregulation and genetic mutations in blood cancers, some of which are linked to immune responses;
• A case-control study showed that obesity at all ages was an independent risk factor for chronic myeloid leukemia with a significant dose-response effect;
• Several promising anticancer agents and immunotherapy treatments have been shown effective in animal models and clinical trials (including: BL22, bortezomib, alemtuzumab, rituximab, Romidepsin, siplizumab) Item Gastrointestinal (GI) Cancer - The Committee is concerned that early diagnosis of most GI cancers is difficult or impossible, especially aggressive GI cancers in young people, and curative treatment options are non-existent at later stages. The Committee encourages NCI to study GI cancers in people age 40 and under, giving emphasis particularly to latestage cancers for whom curative treatment options are unavailable. In addition, the Committee requests NCI to consider developing an interconnected gastrointestinal cancer biorepository with consistent, interoperable systems for collection, storage, annotation, and information sharing. (p.108) Action taken or to be taken In 2009, NCI co-sponsored a workshop on the biology of colon and other cancers in adolescent and young adult populations. Participants examined the biological underpinnings of the rising incidence of colon cancer in this age group and why these young patients often have poorer outcomes than older ones. NCI is developing a study that will accrue patients from both pediatric and adult clinical trial groups that study gastrointestinal (GI) disorders. In addition, adult phase III treatment trials routinely include participants down to age 18 and the data are examined according to patient age.
Individuals with a family history of colorectal cancer (CRC) are at increased risk of the disease: having a first-degree relative with CRC approximately doubles the risk, which increases further with the proportion of relatives affected, particularly if they are diagnosed at an early age. The NCI-established Colon Cancer Family Registry (C-CFR) is an international research infrastructure for investigators interested in conducting studies on hereditary CRC. The C-CFR has biospecimens from more than 11,300 families across the 3 spectrum of risk for colon cancer and is centralizing these samples so that researchers can use the biospecimens for further study.
NCI intramural researchers have started a clinic to study gastrointestinal stromal tumor in children and young adults. The clinic collects tumor tissue, which is tested for known mutations associated with this cancer. In addition to the samples, information from patient histories, physical examinations, and imaging studies is used to develop new treatment regimens for patients who currently have limited options for cure.
An NCI initiative known as the cancer Human Biobank (caHUB) is establishing a centralized specimen bank that will collect high-quality, standardized samples from GI cancers, including colon, pancreatic, and stomach tumors. Using state-of-the-art informatics tools, caHUB will allow data from biospecimens to be paired with other clinical information. NCI-sponsored phase III trials collect other biospecimens and an interconnected GI biorepository inventory summary is being planned. All of these resources will aid investigators in the GI field.
NCI-funded studies are pursuing methods in all age groups to detect early GI cancers, which may be more amenable to treatment than advanced cancers. Scientific reports this year indicate that small molecules known as microRNAs, which can be detected in blood samples, have the potential to help identify patients with early pancreatic cancer and may provide useful biomarkers for colon cancer and predict survival. Another study suggests that mutations in certain genes associated with adding sugar molecules to proteins may cause a predisposition to colon cancer.
Screening for one of the most common types of liver cancer, hepatocellular carcinoma (HCC), may be able to be improved, particularly if the patient has a history of hepatitis. By combining two screening tests, researchers reported this year that they were able to accurately identify more early stage HCC cases.
Item Gynecologic Cancer SPOREs The Committee is encouraged by the success of the gynecological cancer SPORE program. At present there is no available screening test for ovarian cancer to identify the disease at an early stage and improve survival. Given the inadequacies of current tools, there is a pressing need for new effective screening technologies, as well as for the development of new targeted therapies to decrease the mortality and morbidity of this disease. In addition, there is a need for research that is focused on endometrial and uterine cancer, The Committee encourages NCI to support existing gynecologic cancer SPORES as well as to consider increasing their overall number. (p.108, 109) Action taken or to be taken This year, researchers from NCI’s SPORE program, the Early Detection Research Network, and the Prostate, Lung, Colorectal and Ovarian cancer screening trial reported on a rigorous validation study of more than 50 potential markers for detecting early signs of ovarian cancer in blood. The study found that the most accurate marker is CA-125, a protein that is already routinely monitored in women with the disease. Panels of markers 4 tested in the study offered, at best, only marginal improvements in the ability to detect the disease over CA-125 alone although several other candidate markers showed promise, including HE4. This latter protein was discovered in a SPORE program and has recently been approved by the FDA for monitoring cancer recurrence. Other NCI early detection studies include measuring a blood panel of methylation markers and a compound called claudin-4.