The Developmental Therapeutics Program (DTP) is the group in NCI that supports the discovery and development of novel therapeutics for treating cancer. These can be either low molecular weight compounds or biological entities such as antibodies or virus vectors. The low molecular weight compounds can be either novel synthetic compounds or purified natural products.
The aim of the drug discovery efforts is to identify promising therapeutic strategies, especially associated with novel mechanisms of biological action.
The aim of the development efforts is to get the most promising strategies ready for a clinical trial. An additional role for DTP is to provide the cancer research community with as much of the data generated by these activities as possible. This involves generating and documenting data sets and making them available via web pages. The DTP Computer Center (DTPCC) provides computer support, including operations, technical support services, and software development, to the DTP, DCTD, NCI. The DTPCC provides services for many aspects of the DTP's information systems requirements, including data acquisition within the laboratories, data transfer to the Oracle Relational Database Management System (RDBMS), analysis and statistical evaluation, and web publication of experimental results. Computer support is provided for many functions of the DTP, including identifying and scheduling compounds to test, preparing and handling the compounds, performing the experiments, and analyzing experimental results for activity. The primary groups within the DTPCC are the Enterprise and Windows Server support groups, including support for Oracle, OpenVMS, Windows, HPUX and Linux-based servers; the Web Application Development Group, responsible for the creation and maintenance of program web pages and applications, as well as Java and Oracle development activities; the Legacy Applications Development Group, responsible for continued support and maintenance of core components of the existing DTP software infrastructure; the Workstation Support Group, responsible for end-user support of desktop applications; and the Target Structure based Drug Design Group (reported separately), providing expertise in rational drug design, protein modeling, and bioinformatics. The DTPCC hosts several web sites for the Division of Cancer Treatment and Diagnosis (DCTD). These include the DCTD site, the Cancer Diagnosis Program, and the Developmental Therapeutics program site. They will soon host new sites for the Translational Research and Clinical Trials Evaluation Programs. The DTPCC hosts many division initiatives. These include: Document management systems: Successfully installed, configured and deployed the Biblioscape reference management server for DTP. Configured and hosted a second web site for access to the DTP's Laserfiche document management database (https://pdsop.nci.nih.gov). Online-Rapid Access to Interventional Development (e-RAID): Added to the eRAID application a SEP committee review application. The SEP is now able to review all eRAID applications, committee documents, and reviewer comments on-line for each RAID cycle. Compound Submission System (CSS). This application was rewritten to remove the PKI certificate requirements for log in, report viewing, RAID applications, or compound testing submission. A new registration application was written that allows users to create and change their own passwords. One-Dose and In vivo Toxicity Data reports were added to the CSS. Completed MTA legal requirements update to the Compound Ordering System.The DTPCC also implements department initiatives such as: Enhanced laptop security. In compliance with NIH directives, the staff completed the encryption of all laptop computers under the custodianship of the DTPCC. This security measure prevents the loss or compromise of data derived from the DTP's enterprise Oracle database (completed July 2007). DST remediation. Completed daylight savings time (DST) remediation for all servers within the DTPComputer Center (41 servers), bringing servers into compliance with changes mandated by the Energy Policy Act of 2005. Federal Desktop Core Configuration(FDCC): The DTPCC played an instrumental role in implementing the OMB-mandated FDCC security settings. The Web Application Development Group developed and maintains a web-based application suite that functions as a computational tool for drug discovery. This tool is known as PILOT(Pharmacophore Identification and Lead Organization Tool) as a web. This chemoinformatic tool searches for common pharmacophores within a user-specified set of molecules. This effort is the result of a collaboration with the Target-Structure Based Design Group. The DTPCC also provides a Target-Structure Based Design Group (DPTCCTSBDDG). This group provides support to the Information Technology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, in the area of molecular modeling, drug discovery, chemoinformatics, and software development. The majority of the work performed by this group consists of computational methods development and application to DTP-prioritized targets in collaboration with laboratories that are involved in the quantitative testing of lead compounds and the chemical synthesis of drug candidates. Cancer targets of interest include: multiple tubulin sites, CDK's, and recently, RSK protein and topoisomerases. The group has also been tasked with laboratory and computational support of the USAMRIID/NCI-DTP Joint Antibioterrorism Therapeutics Interagency Agreement (IAG). This project has focused on the development of therapeutics for certain Biothreat Level A and B agents that pose the greatest threat due to their infectiousness, relative ease of transmission, or high rate of mortality. Currently under investigation in the IAG are: Bacillus anthracis toxins, Botulinum neurotoxins, Ricinus communis or ricin toxin, Staphylococcal enterotoxins, and Filoviridae targets (Ebola and Marburg). The IAG began in March of 2001 and all of the staffing, procurement, and subcontract management have been executed through the TSBDDG. All of the data and techniques developed through the IAG efforts have been important for not only generating therapeutics to counter biological weapons, but have also resulted in more effective and efficient molecular modeling services for cancer researchers requesting NCI support with regard todrug design and development.
