National Cancer Institute - NCI Division of Cancer Treatment and ...
National Cancer Institute - NCI Division of Cancer Treatment and ... National Cancer Institute - NCI Division of Cancer Treatment and ...
Drug Discovery T O O L S , P R O D U C T S , A N D R E S O U R C E S Natural Products Repository http://dtp.nci.nih.gov/branches/npb/ repository.html DTP’s Natural Products Repository is the world’s largest storehouse of natural products. It houses close to 170,000 extracts from samples of more than 70,000 plants and 10,000 marine organisms collected from more than 25 countries, plus more than 30,000 extracts of diverse bacteria and fungi. The natural products stored in DTP’s repository are screened against the NCI human tumor cell line assay for potential anticancer activity shortly after their collection. So far, about 4,000 natural-source extracts have shown in vitro activity against human cancer cells, making them worthy of further study by DTP researchers. The Natural Products Repository, administered by the Natural Products Branch, provides extramural researchers with natural products extracts for testing against any human disease. Synthetic Products Repository http://dtp.nci.nih.gov/branches/dscb/ repo_open.html Since this repository began about 40 years ago, more than 500,000 proprietary and nonproprietary compounds have been submitted to the program. In addition to being a repository for NCI screens, the repository distributes compounds for research purposes both as specific vialed compounds and in plated sets for highthroughput screening. DTP’s plated sets have been instrumental in the discovery of compounds that enhance antilymphoma activity, nucleic acid antagonists with anti-HIV activity, and inhibitors of angiogenin—to name a few important advances. The Synthetic Products Repository has recently developed a plated set to help evaluate drugs in combination. NCI’s Pediatric Drug Development Group will be one of the first groups to use the new plated sets; the results of the studies will be posted on DTP’s open-use Website at: http://dtp.nci.nih.gov. DCTD Tumor/Cell Line Repository http://dtp.nci.nih.gov/branches/btb/ tumor-catalog.pdf Since the early 1960s, DCTD has maintained this low-temperature repository, which holds transplantable in vivo–derived tumors and in vitro–established tumor cell lines from an assortment of species. The repository serves as a resource for viable, contaminant-free experimental tumor lines, many of which are not obtainable elsewhere. Researchers can access these materials under a material transfer agreement. D E V E L O P M E N T A L T H E R A P E U T I C S P R O G R A M ■ 105
DTP oversees animal-production facilities that produce inbred and hybrid strains of rats, mice, and guinea pigs. This program provides researchers nationwide with genetically defined, pathogen-free laboratory animals. Animal Production http://dtp.nci.nih.gov/branches/btb/ services.html#AnimalProduction DTP’s Biological Testing Branch oversees animal-production facilities that produce inbred and hybrid strains of rats, mice, and guinea pigs. This program provides researchers nationwide with genetically defined, pathogen-free laboratory animals as well as animal-related services such as jugular vein cannulations, vasectomies, ovariectomies, and castrations. In 2005, the branch distributed 1,473,062 rodents to about 1700 investigators at 240 institutions. In Vitro Screening: The Human Tumor Cell Line Assay http://dtp.nci.nih.gov/branches/btb/ ivclsp.html In 1985, the hypothesis was put forward that a human tumor cell line screen could help investigators discover celltype–specific agents with clinical activity against solid tumors. The emerging reality was that while correlation of in vitro histology to clinical activity is poor, the pattern of cellular sensitivity and resistance of the cell lines to the drug correlated with molecular target expression. In response, DTP developed a cell-line– based screen representing the major classes of solid tumors. That allowed relatively inexpensive and rapid testing of potential therapeutic agents against broad panels of human tumors that could be adapted to the needs of natural product screening. 106 ■ P R O G R A M A C C O M P L I S H M E N T S 2 0 0 6 ■ ■ ■ Since April 1990, DTP has used the human tumor cell line in vitro screen as its primary assay with follow-up in vivo evaluation in the hollow fiber assay. The screen is currently composed of 59 human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. These cell lines were selected partly on pragmatic terms: those selected behaved best under typical assay conditions. The screen was designed so that for each compound tested, both the absolute and the relative sensitivities of individual cell lines were reproducible to the extent that a characteristic profile or fingerprint of cellular response was generated. Although the particular inhibitory response of a single cell line might be relatively uninformative, the pattern of response of the cell lines as a group can be used to rank a compound according to the likelihood of sharing common mechanisms. The COMPARE algorithm (a computer program) qualifies this pattern and searches an inventory of screened agents to compile a list of the compounds that have the most similar patterns of cellular sensitivity and resistance. Extramural researchers who wish to access this service should complete an online submission form: http://dtp.nci. nih.gov/compsub/index.html. Pure compounds must be of known molecular structure, and the investigator is required to enter the molecular structure on the online submission form before sending samples of the test compound. Additional
- Page 59 and 60: C U R R E N T F U N D I N G O P P O
- Page 61 and 62: Quick-Trials for Imaging and Image-
- Page 63 and 64: Association of American Cancer Inst
- Page 65 and 66: Food and Drug Administration and Ce
- Page 67 and 68: Dr. Edward A. Neuwelt, Oregon Healt
- Page 69 and 70: Virtual Colonoscopy Training Collec
- Page 71 and 72: Not only does CTEP identify promisi
- Page 73 and 74: The Clinical Trials Cooperative Gro
- Page 75 and 76: of pediatric cancers and therapeuti
- Page 77 and 78: the front line treatment of chronic
- Page 79 and 80: Quick-Trials for Novel Cancer Thera
- Page 81 and 82: Industry Collaborators Agent Name 7
- Page 83 and 84: Industry Collaborators Agent Name 7
- Page 85 and 86: NCI Visuals Online, George McGregor
- Page 87 and 88: provided for use in this clinical t
- Page 89 and 90: with or without bevacizumab (NSC #
- Page 91 and 92: Oxaliplatin-Based Regimen Permits S
- Page 93 and 94: egular checkups to look for lymph-n
- Page 95 and 96: NCI Visuals Online. Human lymphoma
- Page 97 and 98: T O O L S , P R O D U C T S , A N D
- Page 99 and 100: ■ Clinical Trials Monitoring Bran
- Page 101 and 102: DTP’s staff and administered gran
- Page 103 and 104: therapeutics. Proposed exploratory
- Page 105 and 106: M A J O R O N G O I N G I N I T I A
- Page 107 and 108: National Cancer Institute. discover
- Page 109: C U R R E N T F U N D I N G O P P O
- Page 113 and 114: disease can require considerable in
- Page 115 and 116: National Cancer Institute. commerci
- Page 117 and 118: The Type 1 Diabetes Rapid Access to
- Page 119 and 120: H I S T O R Y - M A R K I N G E V E
- Page 121 and 122: With this approach, patients are no
- Page 123 and 124: This included a camptothecin deriva
- Page 125 and 126: RRP supports research involving a v
- Page 127 and 128: Laredo Medical Center, Laredo, TX h
- Page 129 and 130: With TELESYNERGY® as a link, healt
- Page 131 and 132: Radiation Bioterrorism Research and
- Page 133 and 134: Enhanced Radiosensitivity The Molec
- Page 135 and 136: M E E T I N G S A N D W O R K S H O
- Page 137 and 138: Cancer Imaging Program 132 ■ P R
- Page 139 and 140: Cancer Therapy Evaluation Program,
- Page 141 and 142: Developmental Therapeutics Program,
- Page 143 and 144: Developmental Therapeutics Program,
Drug Discovery<br />
T O O L S , P R O D U C T S , A N D R E S O U R C E S<br />
Natural Products Repository<br />
http://dtp.nci.nih.gov/branches/npb/<br />
repository.html<br />
DTP’s Natural Products Repository is the<br />
world’s largest storehouse <strong>of</strong> natural products.<br />
It houses close to 170,000 extracts<br />
from samples <strong>of</strong> more than 70,000 plants<br />
<strong>and</strong> 10,000 marine organisms collected<br />
from more than 25 countries, plus more<br />
than 30,000 extracts <strong>of</strong> diverse bacteria<br />
<strong>and</strong> fungi. The natural products stored<br />
in DTP’s repository are screened against<br />
the <strong>NCI</strong> human tumor cell line assay for<br />
potential anticancer activity shortly<br />
after their collection. So far, about 4,000<br />
natural-source extracts have shown in vitro<br />
activity against human cancer cells, making<br />
them worthy <strong>of</strong> further study by DTP<br />
researchers.<br />
The Natural Products Repository, administered<br />
by the Natural Products Branch, provides<br />
extramural researchers with natural<br />
products extracts for testing against any<br />
human disease.<br />
Synthetic Products Repository<br />
http://dtp.nci.nih.gov/branches/dscb/<br />
repo_open.html<br />
Since this repository began about 40 years<br />
ago, more than 500,000 proprietary <strong>and</strong><br />
nonproprietary compounds have been<br />
submitted to the program. In addition<br />
to being a repository for <strong>NCI</strong> screens, the<br />
repository distributes compounds for<br />
research purposes both as specific vialed<br />
compounds <strong>and</strong> in plated sets for highthroughput<br />
screening.<br />
DTP’s plated sets have been instrumental<br />
in the discovery <strong>of</strong> compounds that<br />
enhance antilymphoma activity, nucleic<br />
acid antagonists with anti-HIV activity, <strong>and</strong><br />
inhibitors <strong>of</strong> angiogenin—to name a few<br />
important advances.<br />
The Synthetic Products Repository has<br />
recently developed a plated set to help<br />
evaluate drugs in combination. <strong>NCI</strong>’s<br />
Pediatric Drug Development Group will<br />
be one <strong>of</strong> the first groups to use the new<br />
plated sets; the results <strong>of</strong> the studies will<br />
be posted on DTP’s open-use Website at:<br />
http://dtp.nci.nih.gov.<br />
DCTD Tumor/Cell Line Repository<br />
http://dtp.nci.nih.gov/branches/btb/<br />
tumor-catalog.pdf<br />
Since the early 1960s, DCTD has maintained<br />
this low-temperature repository,<br />
which holds transplantable in vivo–derived<br />
tumors <strong>and</strong> in vitro–established tumor cell<br />
lines from an assortment <strong>of</strong> species. The<br />
repository serves as a resource for viable,<br />
contaminant-free experimental tumor<br />
lines, many <strong>of</strong> which are not obtainable<br />
elsewhere.<br />
Researchers can access these materials<br />
under a material transfer agreement.<br />
D E V E L O P M E N T A L T H E R A P E U T I C S P R O G R A M ■ 105
Change language