National Cancer Institute, Research Contracts Branch, ESS, Executive Plaza South, Rm. 620, 6120 Executive Blvd., MSC 7224, Bethesda, MD 20892-7224

A -- IN VIVO EFFICACY IN DISEASE-RELATED MODELS SOL N01-CM-97017-09 DUE 081198 POC Mary E. Landi O'Leary; Contracting Officer; 301-435-3812 WEB: Research Contracts Branch/Current Request for Proposals, http://rcb.nci.nih.gov/rfp.htm. E-MAIL: Mary E. Landi O'Leary, ml186r@nih.gov. ELECTRONIC RFP ANNOUNCEMENT, POTENTIAL OFFERORS WILL BE RESPONSIBLE FOR DOWNLOADING THEIR OWN COPY OF THE SOLICITATION AND AMENDMENTS. The Developmental Therapeutics Program (DTP), DCTD, NCI, is interested in establishing a Master Agreement pool. Contractors selected for award of a MA may be solicited to address the following objectives. First, to define the capacity of candidate compounds to affect molecular targets relatable to compound efficacy in a series of pre-existing, robust, in vivo models suitable for immediate use, representing known important pathways in neoplasia; second, to validate methodologies that would assess molecular targets affected by drug candidates which could be readily "translated" to the clinical setting; and third, place these actions of the compound in the context of conventional measures of tumor shrinkage or growth delay. Following the identification of appropriate drug leads, and taking into account previously established pharmacologic and biologic features of the test molecules, study in an in vivo model will be undertaken to define not only effects on cell proliferation as an endpoint, but also effects of the drug on its putative molecular target or cellular process of reference. Examples might include models engineered to be relevant to cell cycle checkpoint control e.g., Rb,53), apoptosis (e.g., bcl2 family genes), molecularly defined but cell type-related (e.g. mutated androgen receptor in prostate cancer) or process-related (e.g., angiogenesis, endocytosis, cell motility, etc,) disease endpoints. Spontaneous, genetically modified or induced (e.g. knockout), orthotopic and xenotransplanted models are all of potential interest, provided that their biological characteristics and correlation with relevant issues in the pathogenesis of neoplasia are clearly apparent. The results of a project area supported by this Master Agreement would be evidence that a candidate compound could indeed affect a clearly defined molecular endpoint. This information would be of critical importance in designing initial activities where the endpoint of the compound's action may not be classical cytotoxic effect, but for example cytostasis or differentiation. This activity would support a new way of thinking about cancer drug action, which has modulation of important molecular targets or cellular processes as endpoints for early clinical trials. Master Agreements will be awarded to all respondents whose technical proposal is considered acceptable. The Master Agreement award is non-monetary and is exclusively for the purpose of compiling a pool of contractors who are pre-qualified to perform services. This acquisition is for a five year Master Agreement Pool in support of the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, NCI located in Rockville, Maryland. Each Master Agreement holder will be eligible to compete for future contract awards to carry out specific tasks. Master Agreement holders receiving a contract award will be selected through this pool, based ontechnical merit and on budgetary considerations for the specified tasks involved. The Master Agreement mechanism is a pre-qualification to enable qualified sources to compete for and perform future contracts which will be awarded based on Request for Proposal (RFPs). The MA itself is unfunded. The obligation of funds shall be accomplished solely through the award of a contract. All responsible sources meeting these criteria are encouraged to submit a proposal and will be considered by the NCI. All proposals should reference N01-CM-97017-09 The RFP may be accessed through the Research Contracts Branch Home Page by using the following Internet address: http://rcb.nci.nih.gov/rfp.htm. It is the offeror's responsibility to monitor the above internet site for the release of this solicitation and amendments, if any. POTENTIAL OFFERORS WILL BE RESPONSIBLE FOR DOWNLOADING THEIR OWN COPY OF THE SOLICITATION AND AMENDMENTS. Point of contact: Mary E. Landi O'Leary; Electronic mail address: OLEARYM@rcb.nci.nih.gov; Fax 301-480-0241. No collect calls will be accepted. (0148)

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