CANCER DRUG DISCOVERY: DIVERSITY GENERATION AND SMART ASSAYS Release Date: April 3, 1998 RFA NUMBER: CA-98-009 P.T. National Cancer Institute Letter of Intent Receipt Date: October 21, 1998 Application Receipt Date: November 18, 1998 PURPOSE The Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI) invites Program Project grant applications (P01s) proposing a) innovative approaches to the generation of structural diversity, such as combinatorial synthesis, parallel synthesis or genetic manipulation of biosynthetic pathways in producer organisms and b) smart assay development for cancer drug discovery (Nature, Supplement to Volume 384, Issue No. 6604, November 7, 1996). Applications responsive to this Request for Applications (RFA) will bring together multidisciplinary teams of chemists and biologists who will propose novel approaches to the discovery of compound classes potentially active against cancer. This initiative seeks to catalyze the formation of such teams to exploit opportunities presented by the rapidly advancing state of contemporary chemistry and biology. Participants may come from the same or different departments in the same academic institution, or from different institutions, or from (an) academic department(s) and industry. Approaches may include the application of synthetic or biosynthetic combinatorial approaches to generate libraries of novel structures. Conceivably both techniques might be utilized by different components of the same research group, and active products of the biosynthetic approach may serve as novel scaffolds for elaboration using combinatorial synthetic technology. In close association with the generation of compound libraries, applicants should also propose the development or application of novel assays directed at molecular events or targets important in the neoplastic process and suitable for assaying the compound libraries. Applicants may employ any biological system that is likely to be informative in the context of this initiative. Reliance solely on anti- proliferative or cytotoxic assays which do not provide information on vulnerabilities of selected targets will not be responsive to this RFA. Manipulation of structures based on clinically-approved anticancer drugs also will not be considered responsive to the RFA. A former RFA with the same title (CA-97-006) was published on May 9, 1997 in the NIH Guide for Grants and Contracts, and several awards are being negotiated as a result of that competition. Because of the promise of the new approaches described above for drug discovery and the rapidly changing and improving technology in creating new molecules and novel assays, this effort is being recompeted. A reissuance will encourage the formation of new groups, especially those in the emerging area of biosynthesis, and will allow the previously unsuccessful groups another opportunity to compete. Although it is recognized that the discovery and development of effective therapies can be a long and arduous process involving many steps, including lead discovery and optimization and evaluation of the most promising materials in pharmacology, toxicology, formulation and other studies to identify candidates for clinical development, NCI is prepared to assist any awardee in bringing new products to clinical trial and has developed processes, such as the Decision Network process, to expedite the translation of laboratory discoveries to clinical evaluation (Edward A. Sausville, "Working with the National Cancer Institute", Anticancer Drug Development Guide: Practical Screening, Clinical Trials, and Approval edited by B. Teicher, Humana Press Inc., Totowa, NJ, 1997, pp. 217-226) (available from Dr. Wolpert listed under INQUIRIES). Industrial partners also may be interested in supporting developmental activities, such as large-scale production, which are beyond the scope of the RFA. The goal of this RFA is to identify and optimize lead structures. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Cancer Drug Discovery: Diversity Generation and Smart Assays, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit, and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Applications may not be submitted by foreign institutions, however, an application from a domestic institution may include foreign components as research projects or core activities, as defined below under MECHANISM OF SUPPORT. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as Principal Investigators (PIs). MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) program project grant (P01) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to the RFA may not exceed five years. The earliest expected award date is April 1999. Because the nature and scope of the research proposed in response to the RFA may vary, it is anticipated that the size of individual awards will vary. An application should be constructed using the P01 application guidelines of the NCI, which are available from the NCI Referral Officer as described below under APPLICATION PROCEDURES. The P01 mechanism is designed to support multiple, interacting projects focused on a central theme. P01s must have a minimum of three projects and may include cores. A core is a separately budgeted component of a P01 that provides essential facilities or services to two or more of the proposed research projects. A core may not count as one of the three research projects. Cost sharing arrangements with industry are encouraged, but detailed project descriptions must be provided even if no funds are requested for a project or core activity. P01s may support projects that are performed at multiple sites but coordinated by a single Principal Investigator at the grantee institution. PIs will be responsible for the planning, direction and execution of the proposed project. An award will be made only to the PI"s institution. All activities will be coordinated through an administrative core located at the PI"s institution. An administrative core is recommended, especially if multiple institutions are involved in the P01. This RFA is a one-time solicitation. Future unsolicited continuation applications will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures. Except as otherwise stated in the RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publications No. (OASH) 90-50-000, revised April 1, 1994. FUNDS AVAILABLE The NCI has set aside $3.00 million total costs (direct plus facilities and administrative costs) for the first year of funding, and the anticipated number of new awards is expected to be at least three. The number of awards and level of support is dependent on the receipt of a sufficient number and diversity of applications with high scientific merit. It is expected that most awards will not exceed $950,000 total costs (direct plus facilities and administrative costs) for year one with no more than a 3% per year increase for future years. Exceptionally meritorious applications may be funded at a higher level provided the budget is adequately justified and considered reasonable by peer review. Budget requests should be carefully justified and commensurate with the needs of the project. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Recent developments in chemistry and biology suggest possibilities for an entirely new vision for cancer drug discovery. The unprecedented power of chemical and biological combinatorial techniques have made it possible to generate impressive structural variation in the laboratory. At the same time the fast-paced identification of gene products, gene sequences, and pathways relevant to neoplasia enables the creation of novel assays for biological functions relevant to cancer. These should permit a much more informative exploration of "diversity space" than has been possible previously for biological activities with therapeutic implications. Implementation of such assays on a large scale is now much more practical by remarkable engineering advances in robotics, miniaturization, and information processing. NCI proposes the present initiative to create multidisciplinary teams for drug discovery featuring close collaboration between chemists and biologists to explore novel approaches that will take full advantage of the opportunities presented by scientific advances. For many years, there have been extensive programs for the acquisition of novel structures from both natural and synthetic sources and for testing extracts and compounds in in vivo and in vitro screens for antiproliferative activity. This approach has been productive and has, in fact, yielded most of the agents in the current armamentarium (platinum complexes, nucleoside analogs, antifolates, vinca alkaloids, taxanes and camptothecin derivatives). The current state of the relevant science and technology suggests now, however, that a very different paradigm for the discovery of anticancer agents might be at hand. It seems clear, for example, that a vast diversity of chemical structures can be generated in the laboratory over surprisingly short time frames. There is no consensus at present that the degree of diversity derivable from laboratory experiments yet approximates what can be found in nature, but experience to date suggests that many millions of distinct structures can result from synthetic efforts extending over only a few months. In a similarly revolutionary vein, assays for biological relevance can now be designed to give information not only about phenotypic alteration, such as growth arrest or cell death, but about the effect on particular molecular targets of pathways known or suspected to have biological relevance to cancer. Research Goals and Scope Since a multidisciplinary collaboration is envisioned, successful applicants must present plans for effective team communication and coordination of effort covering development, implementation, and conduct of all aspects of the research program from generation of novel structures and screening data to data management and decision-making. Although it is desirable that team members can demonstrate evidence of previous collaborations with one another, previous collaborations are not a requirement of the RFA. Structural diversity may be generated by a variety of approaches, including combinatorial or parallel synthesis, or by genetic manipulation of biosynthetic pathways in producer organisms. The molecules produced may represent de novo collections of novel structures, or efforts to optimize lead structures with promising but incompletely developed potential. In no case should the compounds to be studied represent iterations of structures already FDA-approved for use in the treatment of human malignancy. An applicant may propose the generation of various types of structures, such as low molecular weight organic molecules or larger products, such as peptides, based on any reasonable hypothesis for the generation of novel anticancer agents. Although the focus of this RFA is on generating and optimizing lead structures useful for the treatment of cancer, other factors, such as drug delivery to the target site and ease of production, will determine the ultimate success of a product. Combinatorial Organic Synthesis: A key feature of combinatorial techniques is that compound synthesis can be designed such that a range of structures can be produced simultaneously as mixtures in the same reaction vessel or individually in parallel using semi-automated synthesis. The repetitive nature of the synthetic processes involved in most combinatorial applications lends itself to automation or semi-automation. This key feature means that the bench chemist can singlehandedly prepare tens, hundreds, or thousands of compounds of known structures in the time that it would take to prepare only a few pure entities by orthodox methodology. Combinatorial technology can be practiced in either a solution or solid-phase format. Solution techniques utilize methods essentially similar to standard methods for the synthesis of single compounds, except that instead of using one well-defined reaction partner of each type per reaction, mixtures of several known reaction partners are added as building blocks, thus resulting in mixtures of analogs. The type of the chosen chemical reaction and the number of reactants depend on the nature of the desired structures. These mixtures may not be purified elaborately but are directly subjected to screening against the desired target (e.g., receptor, enzyme, antibody, cell). The chemistry is then repeated a few times in batches using different but well defined mixtures of reaction partners, and the products isolated and screened. In order to identify the leads, the chemistry is repeated several times using fewer reaction partners in each run, and the products are screened. This deconvolution process is repeated until the most potent lead is identified. In solid-phase approaches, pin or bead techniques permit the synthesis of different molecules on each pin (i.e., "one molecule-one bead"). The products of solid-phase synthesis can be cleaved from the backbone matrix for solution screening (which is essential when the screening target is a cell), or the most active molecules displayed on the polymer surface may be detected using molecular targets (receptor, enzyme, antibody) pre-tagged with a means of detection (visible color, fluorescence, radioactivity, chromophore, etc.) and then isolated and identified. Manipulation of Biosynthetic Pathways: Biosynthetic approaches to generating diversity may also be used to produce large numbers of novel structures. Recent progress has focused on the creation of hybrid antibiotics through genetic engineering (Katz et al., Ann. Rev. Microbiol 47: 875-912, 1993) and in the production of novel structures based on genetic manipulation of the aromatic polyketide biosynthesis pathways in prokaryotic microorganisms (Khosla et al., Nature 375: 549-554, 1995). A set of programming rules, which helps to predict the potential structures of novel polyketides produced by strains carrying these recombinants, has begun to emerge and forms the basis for the use of biosynthesis as a route to new aromatic polyketides. Polyketides are described in biosynthetic rather than structural terms. Broadly, this category comprises structures derived wholly or partly from poly- -ketomethylene chains, and includes a rich source of bioactive molecules, including antibiotics, such as the tetracyclines, anticancer agents, such as daunomycin, and immunosuppressants, such as FK506 and rapamycin. Outside the polyketide area there is still much to be learned in elucidating the biosynthetic pathways of secondary metabolites from other microbes, plants, or marine organisms. The exploration of biosynthetic pathways in plants and marine organisms has been much more difficult than that of their prokaryotic counterparts because of slower growth rates, the often more complicated structures of the secondary metabolites, the existence of multi-gene pathways that are not clustered in the genome, and the presence of enzyme- inactivating constituents. Definition of the pathways involved in the production of non-polyketide-derived structures especially by employing cell culture and modern molecular biologic techniques may also be tied to the generation of structural diversity. Recombinant technology has paved the way for characterizing the genomic information of new species and strains of microorganisms which were deemed "unculturable" previously and has opened a huge resource for chemical diversity. Applications which define and manipulate biosynthetic pathways but do not address the generation of chemical diversity will not be considered responsive to this RFA. Although it is recognized that biosynthetic approaches may not generate the volume of compounds possible with synthetic approaches, nature has produced many interesting "scaffolds" and the percentage of biologically active materials may be higher. Applications which propose a combination of combinatorial biosynthetic and synthetic approaches are especially encouraged. Novel Screening Approaches: A "smart" assay may be operationally defined as a screening system that by its very operation conveys information about new chemistry or biology of "hits" in the system. For example, an assay tailored to produce a specific readout regarding downregulation of the RAS signaling pathway could be considered "smart". A variety of intervention points in a pathway may regulate a disease process. Assays of interest may couple the use of a cloned and expressed target protein or a nucleic acid sequence in tandem with a chemical or biosynthetic process that generates molecules for further study. Alternatively, the use of genetically definable yet underexplored organisms such as yeast, Drosophila, or C. elegans, production of expression vectors that may operate only in the presence of a compound with the desired properties, development of detection techniques based on novel patterns of molecular recognition, or strategies that require the operation of a particular molecular target as a basis for detection would all be examples clearly responsive to the RFA. In vivo studies are not required in this initiative, however, limited "proof of concept" experiments may be proposed and are encouraged depending on the needs of the project. Expensive toxicology tests, such as those required for the submission of Investigational New Drug Applications to the Food and Drug Administration, are beyond the scope of the RFA. Applicants may propose existing assays, new assays, or a combination of both types. However, rather than merely proposing a collection of assays, applicants should endeavor to propose assays that fit a theme and test a hypothesis with relevance to cancer. SPECIAL REQUIREMENTS This initiative requires the assembly of inter-disciplinary teams with the skills needed to pursue successfully the generation of novel structures, their screening against defined biological or biochemical target(s), and the optimization of lead structures. Since the team may include investigators from more than one institution, "letters of intent to collaborate with the applicant organization" signed by the appropriate institutional official from each participating organization must be included in the application. Submission of formal collaborative documents can be delayed until time of award. The NCI recognizes that source countries retain interests in samples collected in their domains. All applicants who propose to use organisms or other naturally- derived materials of foreign origin in their studies must provide a plan, signed by representatives of all participating institutions, for equitable return of a portion of any profits or royalties, or other acceptable forms of compensation, derived from their discoveries to indigenous peoples, research collaborators, cooperating institutions or Governmental entities in the countries of origin, as appropriate to their contributions. It is preferred that this plan be submitted with the application. If this plan is not included as part of the application, it must be submitted as a condition for award to a Program Official to be designated at the time of award. Since the discovery of new anticancer agents may result from these P01 projects, it is essential that applicants provide plans to assure patent coverage. The situation could be complicated since multiple institutions, including industry, may be involved. Each applicant must therefore provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to P.L. 96-517 as amended by P.L. 98-620 and 37 CFR Part 401. Instructions were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. NOTE: A formal statement of Patent Agreement among participants and their institutions, as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, signed and dated by the organizational official authorized to enter into patent arrangements for each participant and participating institution is preferred with the application. If this signed agreement is not included in the application, it must be submitted as a condition for award to a Program Official to be designated at the time of award. Applicants should plan to attend an annual meeting of awardees of this and the previous RFA with the same title to share research findings and to discuss issues of common interest or concern. For budgetary purposes, applicants should budget for two representatives of their P01 to attend an annual meeting at the NIH campus in Bethesda, MD. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all applications submitted in response to this RFA. All investigators proposing research involving human subjects should read the "NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS" that was published in the NIH Guide for Grants and Contracts, March 6, 1998 and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html LETTER OF INTENT Prospective applicants are asked to submit, by October 21, 1998, a letter of intent that includes a descriptive title of the proposed research and a list of titles for the anticipated components of the P01, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to Ms. Toby Friedberg at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 5/95). Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: ASKNIH@od.nih.gov. Applications must conform the guidelines contained in the P01 application guidelines of the NCI (rev 03/97), which are available via the World Wide Web at http://deainfo.nci.nih.gov/ following the path Extramural Activities, to Grant Guidelines and Descriptions, to Research Program Projects and Centers, P-series, to P01 Guidelines. Guidelines are also available from Ms. Toby Friedberg at the address listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817-7710 (for express/courier service) At the time of submission, two additional copies of the application must be sent to Ms. Toby Friedberg at the address listed under INQUIRIES. Applications must be received by November 18, 1998. Applications received after that date will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to the RFA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and responsiveness by the NCI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. The PI may choose to submit the application as an unsolicited, investigator-initiated P01 at the next deadline for competing P01 applications. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Special Review, Referral and Resources Branch (SRRRB), Division of Extramural Activities, NCI. As part of the initial merit review, a process may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non-competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. Because of the time allotted for the review, no site visits are planned. Therefore, it is important that all information necessary for an informed review be included in the written application by the due date. The Scientific Review Administrator (SRA) will contact the PI for the opportunity to provide supplementary material, such as recent publications, before the review. No material should be submitted unsolicited. Review Criteria The five criteria to be used in the evaluation of grant applications are listed below. The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. The reviewers will comment on the following aspects of the application in their written critiques in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered by the reviewers in assigning the overall score weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. 1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? 2. Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the screens relevant to the neoplastic process? Is the decision-making process adequate for identifying and optimizing leads? Are the plans for data storage and manipulation adequate? Are the plans for multidisciplinary collaboration and coordination adequate? 3. Innovation. Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? 4. Investigator. Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? 5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? The initial review group will also examine: the appropriateness of proposed project budget and duration, the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects, the adequacy of plans for including children as appropriate for the scientific goals of the research, or justification for exclusion, the provisions for the protection of human and animal subjects, and the safety of the research environment. Review criteria used to evaluate P01 applications will also be used in the review of these applications. Peer review of the overall scientific and technical merit emphasizes a synthesis of two major aspects: 1) review of the P01 as an integrated effort focused on a central theme and 2) review of the merit of individual research projects and core components in the context of the proposed P01. Applicants are encouraged to study the evaluation criteria cited in the P01 guidelines (referred to in APPLICATION PROCEDURES) before preparing their applications. The following sections from the P01 guidelines will apply to the review of this RFA: REVIEW CRITERIA FOR THE OVERALL PROGRAM, REVIEW CRITERIA FOR THE PROGRAM AS AN INTEGRATED EFFORT, REVIEW CRITERIA FOR PROJECTS, REVIEW CRITERIA FOR CORE(S) (if applicable), and ADDITIONAL CRITERION FOR AMENDED APPLICATIONS (if applicable). AWARD CRITERIA The earliest date of award is July 1, 1999. The following will be considered in making funding decisions: o Scientific merit as determined by peer review o Diversity of applications and programmatic priorities o Availability of funds o Responsiveness to the goals and objectives of the RFA. Schedule Letter of Intent Receipt Date: October 21, 1998 Application Receipt Date: November 18, 1998 National Cancer Advisory Board: June 1999 Anticipated Award Date: July 1, 1999 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Biosynthetic Issues Yali Hallock, Ph.D. Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, Room 841, MSC 7456 Bethesda, MD 20892-7456 Telephone: (301) 496-8783 FAX: (301) 402-5200 Email: yh11c@nih.gov Chemistry Issues John A. Beisler, Ph.D. Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, Room 841, MSC 7456 Bethesda, MD 20892-7456 Telephone: (301) 496-8783 FAX: (301) 402-5200 Email: beislerj@dtpepn.nci.nih.gov Screening Issues and Scope of Studies Mary K. Wolpert, Ph.D. Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, Room 841, MSC 7456 Bethesda, MD 20892-7456 Telephone: (301) 496-8783 FAX: (301) 402-5200 Email: wolpertm@dtpepn.nci.nih.gov Direct inquiries regarding review issues, requests for the NCI P01 Guidelines, and address the letter of intent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard, Room 636, MSC 7407 Bethesda, MD 20892-7407 Rockville, MD 20852-7407 (for express/courier service) Telephone: (301) 496-3428 FAX: (301) 402-0275 Email: FRIEDBET@DEA.NCI.NIH.GOV Direct inquiries regarding fiscal matters to: Ms. Cynthia W. Mead Grants Administration Branch National Cancer Institute 6120 Executive Boulevard, Room 243, MSC 7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, ext. 254 FAX: (301) 496-8601 Email: meadc@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Parts 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


NIH Office of Extramural Research Logo
   Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) 		  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.