Release Date:  February 16, 2000

PA NUMBER:  PAR-00-062
National Cancer Institute

Letter of Intent Receipt Date:  June 6, 2000
Application Receipt Date:       July 18, 2000


The National Cancer Institute (NCI) defines new, extraordinary research 
opportunities through stated goals in a "Bypass Budget".   Among the 
priorities of the 2001 Bypass Budget was to identify and use molecular targets 
for the discovery and clinical testing of new anticancer agents based on the 
molecular mechanisms that underlie neoplastic transformations, cancer growth 
and metastasis.  Accordingly, the Developmental Therapeutics Program, Division 
of Cancer Treatment and Diagnosis, National Cancer Institute (NCI), and the 
Chemoprevention Agent Development Research Group,  the Division of Cancer 
Prevention, NCI  invite competitive supplement applications for existing NIH 
grants to exploit molecular targets for drug discovery.  New insights into our 
understanding of cancer cell biology provide a new opportunity for a 
fundamental re-ordering of approaches to cancer drug discovery.  Rather than 
depending on in vitro and in vivo screens for antiproliferative activity, 
investigators can now focus on new molecular targets and pathways essential 
for the development and maintenance of the cancer phenotype.  As a result, the 
NCI is reorganizing its drug development programs from early drug discovery 
phases to the conduct of clinical trials in order to bring forward new types 
of agents based on strong rationales.  The plan also involves changes in the 
clinical evaluation of new agents that will include appropriate measurements 
to verify target modulation.

In addition to this announcement, the NCI announces following three related  
initiatives in molecular target drug discovery for cancer treatment and 
prevention:  Cooperative Agreement (U01) applications (see which are 
suitable for more mature projects defined by preliminary data;  Small Business 
Innovation Research (SBIR) and Small Business Technology Transfer Programs 
(STTR) (see which 
are directed to those of the small business community who need research 
assistance in launching commercial products;  Exploratory/Development Grant 
(R21) awards ( for 
pilot projects for which preliminary data are lacking that would make the 
project competitive for a regular research grant.  See the Home Pages of 
either the Developmental Therapeutics Program ( or the 
Chemoprevention Agent Development Group( for further 
information or contact individuals listed under “INQUIRIES” of this PA.  
Further information on research opportunities regarding molecular targets in 
drug discovery can be found in the NCI ByPass Budget, The Nation’s Investment 
in Cancer Research: A Budget Proposal for Fiscal Year 2001 at

The purpose of this Program Announcement (PA) is to reorganize the “front end” 
or gateway to drug discovery.   Investigators are being asked to identify a 
novel molecular target, to validate the target as a basis for cancer drug 
discovery, or to develop an assay for the target.  Given the fact that some 
investigators may already have considerable preliminary data on a signaling 
pathway, they nevertheless may not have focused on the point of greatest 
vulnerability in the pathway and therefore, perhaps the optimal point of drug 
attack.  This PA would support an investigator to validate a target and/or 
develop an assay based on the target.  Applicants may address targets related 
to the treatment of established cancers, or the prevention of molecular 
changes which may cause cancer.  Investigators may use their own creativity in 
defining their approach.  For example, some may prefer to 1) use a genetic, 
structural biology or molecular biology approach to target 
identification/validation using information from genetic studies or studies of 
pathways, whereas others may prefer to 2) identify the function of a cellular 
target after first finding the target as a result of exploring binding 
patterns of natural products or other ligands to the novel target.  The PA 
requires that the proposed target(s) in each application be novel and not 
addressed by drugs already approved for clinical use.  

It is envisioned that supplements to funded NIH projects related to target or 
pathway elucidation/validation might enable an extension of projects to 
include goals relevant to drug discovery.  For example, a successful 
competitive supplement could add specific aim(s) such as: expression system 
development to generate large quantities of target protein, target structure 
determination by NMR or X-ray diffraction, development of a target into a drug 
discovery screen, or a chemical library synthesis to explore target validation 

Applications submitted to the NIH will be reviewed by the NCI according to the 
criteria established for this PA as described below under REVIEW 


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 PA, Molecular Target Drug Discovery 
for Cancer, is related to priority areas of human cancer treatment and 
prevention.  Potential applicants may obtain a copy of "Healthy People 2000" 

These competing supplements are directed to existing NCI grantees.  
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 also be submitted by a foreign 
institution.  Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as principal investigators.   
The administrative and funding instrument to be used for these awards is the 
competing supplement to existing NCI-funded research project grants (R01, R15, 
R29, R35, R37, P01 and UO1 mechanisms).  In the case of Program Projects, one 
supplement submission for each constituent project would be permitted.  The 
total project period requested for supplement applications submitted in 
response to this PA may not exceed the number of years remaining in the 
Principal Investigator's active grant at the "start date" of the supplement 
award.  A minimum of two years from the date of the supplement request should 
remain in the parent grant.  The earliest anticipated award date is April 1, 
2001.  Because the nature and scope of the research proposed in response to 
this PA may vary, it is anticipated that the size of supplements will vary, 
but in any case are non-renewable; continuation of projects developed under 
this program must be through other grant mechanisms.   Unless otherwise noted, 
all NIH grants policies apply


The past 20 years have seen an explosion in the understanding of how cancer 
cells work.  Specific molecules have been identified which cause the 
initiation and progressive growth of tumors.  From this work, a fundamental 
re-ordering of the approach to drug discovery and development for the 
treatment and prevention of cancer has emerged.  There is the opportunity to 
move away from screening agents by their effects on tumor cell growth, in vivo 
or in vitro, and targets that have been thoroughly exploited.  While it 
remains true that these methods might continue to be the basis for the 
development of clinically useful agents, these agents may not be the best lead 
compounds that effect a particular pathway of biologic importance specific for 
cancer establishment or progression.  Drugs discovered by these early methods 
have historically demonstrated clear limitations in clinical efficacy.  The 
hope is that drugs targeting new, specific molecular lesions in cancer cells 
will provide more effective therapy or prevention approaches, alone or in 
combination with other agents.  The focus of attention in this new approach to 
cancer drug discovery is a compound’s effect against a novel molecular target, 
or a target operating in a defined biochemical pathway, with the intent of 
causing a gain or loss in function to reverse, stop, or delay cancer 
progression.  The cancer cell selectivity of lead compounds should be enhanced 
by screens based on a novel target or a critical pathway that represents a 
true Achilles heel.

The evaluation of drugs in the clinic which have emerged from these types of 
approaches is beginning.  Examples would include the farnesyl transferase 
inhibitors (FTIs), protein kinase (PK) antagonists of various sorts, matrix 
metalloprotease inhibitors, and growth factor receptor or other effector 
antagonists (endothelin, tamoxifen, TRAIL, etc.).  It is striking that in this 
process the pharmaceutical industry has clearly seized a defining role in 
expeditiously advancing potentially useful compounds to a clinical test.  
However, in each of the instances cited, the pioneering studies on the targets 
to which these drugs are directed occurred largely (if not exclusively) in the 
academic sector.
Objectives and Scope

The goal of these supplemental awards is to expand NCI-funded projects in 
order to enhance the prospects of molecular target discovery and validation 
for cancer prevention or treatment intervention.  Identification of a 
potential target might present varying degrees of difficulty, but validation 
(an indication of a target’s predictive capacity to aid in the selection of 
clinical drugs) is apt to be uniformly more problematic.  Leads for many 
existing clinical drugs were not discovered through the use of  macro-
molecular targets but rather through in vivo or in vitro anti-proliferative 
assays.  Accordingly, the cornerstone of this effort is the validation of 
targets of demonstrated importance.  

The competing supplements to existing NCI-funded grants, herein described, 
should arise from projects that could extend ongoing work toward the 
identification or validation of molecular targets or their development into a 
screening tool.   Approaches and projects appropriate for this PA should be in 
three general areas as follows:

First, investigative activities establishing a molecule as a potential cancer 
drug discovery target can have as its focus any aspect of early dysplasia or 
cancer cell biology that may reveal a vulnerability in the cancer cell.  These 
might include cell cycle checkpoints, DNA repair, cell stress, or cell death 
pathways; cassettes of altered transcription factor activity; or activation of 
pathways allowing cell growth in hypoxic or hypo-vascularized conditions.  
Oncogenic viral targets also would be appropriate.  In fact, any difference 
between a cancer and normal cell could potentially be exploitable as a 
therapeutic maneuver.  Modern science has afforded numerous opportunities to 
demonstrate the likely value of this approach.  These include: (1) engineered 
animals of various sorts (transgene-expressing, knock-out, etc.);  (2) “smart” 
assays designed to give information, not only about phenotypic alteration, 
such as growth arrest or cell death, but also about the effect on particular 
molecular targets of pathways known or suspected to have biological relevance 
to cancer;  (3) array technology, where the action of a candidate drug lead 
against its target can be placed rapidly in the context of expected action 
against other cellular and indeed organ-specific molecules; and (4) cancer 
gene discovery programs, such as the Cancer Genome Anatomy Project (CGAP) ( ), which has identified numerous mutational 
sites in cancer cells, some of which are possibly unique to specific types of 
cancer.  Accordingly, a requirement is to establish that a molecular target 
likely affects important aspects of cancer cell function.

Second, the validation of new molecular targets, with the intent of 
discovering new agents for the treatment or prevention of cancer, is an 
important and necessary activity.  At present, science appears to offer too 
many targets.  Therefore, projects should focus on determining which of these 
numerous potential defects are sites of critical vulnerability which could be 
exploited for intervention.  Ideally one would expect to demonstrate that 
manipulation of the target function would cause a phenotypic change in the 
cancer cell.  Clearly if a prime target is fully validated, such that the 
target can be used to totally exploit a unique difference between a healthy 
and a cancerous cell, control of cancer would then only await the discovery of 
a drug molecule through a systematic screening and/or drug design program; in 
real laboratory experience, validation occurs in stages or degrees.  
Demonstration of some phenotypic or functional change that is desirable, such 
as elimination or reversal of dysplasia, tumor shrinkage or change in a 
validated surrogate marker, would provide evidence of the importance of a 
target.  Approaches to target validation might involve the use of antisense or 
engineered animals, such as transgene-expressing or gene knock-outs.  Small, 
bioactive molecules, obtained either from natural products libraries or from 
chemical libraries, may be used as ligands to select and validate proteins 
from arrays.  If an investigator chooses to utilize crude extracts of natural 
products, as from the NCI Active Repository, expertise must be available for 
chemical fractionation of the extracts.  Thus, validation can be 
conceptualized as a series of milestones.   A proposal to reach validation 
milestones could be responsive to this PA.  There are many good rationales for 
selecting targets, but validation requires considerable imagination and skill 
on the part of the investigator.  Therefore, also responsive to this PA would 
be an insightful and clever validation of a target suggested by others as a 
possible intervention point.  While it is true that the ultimate validation 
can only come from a successful clinical trial, having information on the 
importance of the target prior to the trial should provide important feedback 
in case therapies are ineffective.

Third, the target system should be amenable to conversion into a screen for 
effectors of the target’s function (at minimum on a laboratory scale), or the 
molecular structure determined through biophysical techniques as a prelude to 
drug discovery studies .  These aspects are critical components which would 
form the thrust of any molecularly focused drug discovery effort.  The 
practical nature of drug discovery research is of high importance.  While the 
desirability of this approach might seem obvious, the tools for accomplishing 
this task are only now becoming routinely available.  These include sequence 
information defining the primary structure of relevant target proteins or 
other macromolecules; expression vectors for their large scale production; 
biophysical (e.g. X-ray and NMR) and computational techniques to allow the 
determination of three-dimensional structure; advances in screening technology 
to allow ever increasing speed and efficiency in assessing large numbers of 
candidate structures; and combinatorial chemistry to generate large numbers of 
candidate drug structures.

Supplement requests may include but certainly are not limited to the 

o  Expression of Target:  Successful applicants whose program requires 
production of quantities of expressed target protein for either structure 
elucidation and/or assays will be eligible for supplements to achieve this 
goal.  This could be accomplished either through production at their own 
institution or at a contract research facility using constructs emanating from 
the applicant’s laboratory.  

o  Structural Analysis of Target:  Applicants will be encouraged to describe 
in the application, when it exists, ongoing relationships with structural 
biologists who will be responsible for structure determination using relevant 
physical techniques such as X-ray crystallography or NMR.  At a point in the 
progress of a project when structural analysis might seem appropriate, funds 
for support of biophysical studies may be requested.   Lacking that initial 
collaboration, grantees could obtain supplemental funding through, for 
example, a consortium arrangement with a structural biologist. 

o  Chemistry/Screening:  Following definition of a candidate assay relevant to 
a target, efforts to create libraries of compounds and conduct screening 
activities that are based on the target’s structure may be undertaken.  NCI 
may take the lead in developing specific "made to order" libraries or 
libraries may emerge from existing collections available to NCI.  In the event 
that an MTDD project supplement produces its own libraries, these would remain 
the property of the originator, and maintenance of a voucher collection by NCI 
would not be required.  Screening, in the event it cannot be done in the PI’s 
laboratory, may be conducted by supplementation of the award to include the 
cost of screening.  


Patent Coverage.  Since the discovery of new targets, assays and improved 
anticancer treatments is the objective of this effort and since transfer of 
intellectual property to industrial laboratories for extended developmental 
purposes is facilitated by the existence of adequate patent coverage, it is 
essential that applicants provide plans to assure such coverage. 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.

A formal statement of patent procedures and plan for transfer of materials 
embodying intellectual property to other parties 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 intellectual property arrangements for each applicant and 
collaborators, if any, must be developed.  The signed agreement must be 
submitted prior to award to Dr. John Beisler at the address provided at the 
GCOB web site,  (On the panel, left side, click on 
"Funding", then scroll down to "Staff").

Applicants proposing to access the Natural Products Repository of the NCI must 
obtain and execute the Natural Products Repository Material Transfer Agreement 
prior to receiving an award.  Similarly, applicants proposing to access the 
synthetic repository of the NCI must obtain and execute the synthetic Material 
Transfer Agreement prior to receiving an award.  These agreement forms are 
available at   (On the panel, left side, click on 
"Organization", select "Natural Products Branch", select "Natural Products 
Repository", then scroll down to and select "Material Transfer Agreement").   
For information concerning the NCI synthetic or natural product repositories 
go to the Developmental Therapeutics web site,  (On the 
panel, left side, click on "Samples and Services").  

For applications involving natural products, the applicant must provide a 
formal statement signed by an authorized representative of the applicant 
institution which assures that an equitable portion of royalties or profits 
arising from drugs discovered, if any, will benefit indigenous peoples, 
research collaborators, research institutions or governmental entities as 
appropriate, in the country of origin of the natural product sample from which 
the drug was derived.  Plans for the procurement of proper collection and 
export permits must be provided.  The signed document must be submitted prior 
to award to Dr. Gordon Cragg at the Developmental Therapeutics Program web 
site,  (On the panel, left side, click on 
"Organization", select "Natural Products Branch" then click on "Organization/ 
Staff Directory").

If applicable, a plan must be developed for disposition of natural products 
samples, chemical libraries, etc.  The signed document must be submitted prior 
to award to Dr. John Beisler at the address provided at the GCOB web site,  (On the panel, left side, click on "Funding", then 
scroll down to "Staff").

The four documents listed above will not be included with review material, and 
therefore, will NOT be required at the time of application.  However, awards 
will not be made until they are received and approved by NCI.    

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 
(Section 492B of Public Law 103-43)
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, available on the web at the following URL address:

Investigators may also obtain copies of the policy from the program staff 
mentioned in the GCOB web site,  (On the panel, left 
side, click on "Funding", then scroll down to "Staff").


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 the 
NIH, unless there are clear and compelling scientific and ethical reasons not 
to include them.  This policy applies to all initial (Type 1) applications 
submitted for receipt dates after October 1, 1998.

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 

Prospective applicants are asked to submit, by June 6, 2000, a letter of 
intent that includes a descriptive title of the proposed research, name, 
address, and telephone number of the Principal Investigator, identities of 
other key personnel and participating institutions, and number and title of 
the PAR 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 subsequent applications, the information allows NCI staff to 
estimate the potential review workload and to avoid conflict of interest in 
the review. 
The Letter of Intent is to be sent to a program representative listed under 
INQUIRIES by the letter of intent receipt date listed in the heading of this 

Applicants must use the research grant application form PHS 398 (rev. 4/98).  
Alternatively, NIH intramural project applicants must follow the directions in 
Section 5,  “Additional Instructions for NIH Intramural Project Applicants" 
below.  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, 
E-mail:  PHS 398 application kits are also available at:

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view Internet sites.  Reviewers are cautioned that their anonymity may be 
compromised when they directly access an Internet site (see

SUPPLEMENTS, and the number of this PA must be typed on line 2 of the face 
page of the application form and the YES box must be marked.

The plans below, if appropriate for the proposed work, should be included in 
the application after the LITERATURE CITED section.  Formal agreements signed 
by an authorized representative of the applicant institution will be required 
before award.
o    A plan for patent coverage and licensing; for transfer of material 
embodying intellectual property to other parties;  for resolution of legal 
problems should they arise.

o    A plan for assurance to return benefits to the country of origin in the 
use of natural products.

o    A plan for the disposition of natural products samples and chemical 

Competitive supplement applicants (NIH intramural project applicants must use 
the address in "Additional Instructions for NIH Intramural Project Applicants" 
below) should submit a typewritten, signed 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 (for express/courier service)

At the time of submission, two additional signed photocopies of the 
application must also be sent to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
Bethesda, MD  20892-8239
Rockville, MD  20852 (for express/courier service)

Applications must be received by July 18, 2000.  If an application is received 
after that date, it will be returned to the applicant without review.  The 
Center for Scientific Review (CSR) will not accept any application in response 
to this PA that is essentially the same as a research project application 
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 a 
substantial revision of an application already reviewed, but such an 
application must follow the guidance in the PHS Form 398 application 
instructions for the preparation of revised applications, including an 
introduction addressing the previous critique.


Upon receipt, applications will be reviewed for completeness by CSR and for 
adherence to the guidelines  by NCI.  Incomplete applications will be returned 
to the applicant without further consideration.  

Applications that are complete will be evaluated for scientific and technical 
merit by an appropriate peer review group convened by the Division of 
Extramural Activities of the NCI in accordance with the review criteria stated 
below.  As part of the initial merit review, a process will be used by the 
initial review group in which applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National Cancer Advisory Board.

Review Criteria

The goals of NIH-sponsored research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
Within this framework, the specific goals of this PA are the discovery and/or 
validation of new molecular targets with the potential for developing assays 
for the discovery of new agents to treat or prevent cancer.  For example, 
these supplemental funds may be requested to identify or characterize (de 
novo, or from the literature) a target, to implement a validation plan, or to 
develop a method to render a  validated target into a drug assay.  Meritorious 
projects will include imaginative intervention points and insightful 
validation approaches, which overall will reveal an exploitable site of 
critical vulnerability.

The reviewers will comment on the five criteria listed below in their written 
critiques of the applications 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.  

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?  Is the proposed molecular target of importance to development and 
maintenance of the transformed phenotype?  Is the target new and not one which 
has been the object of other evaluative studies?  What is the likelihood that 
assays using this target will lead to a new class of agents for the prevention 
or treatment of cancer? 

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 
alternate tactics?  How well has the applicant addressed the major goals of 
the PA: identification of a novel target, its validation as an intervention 
point, and assay development?  What is the likelihood that a high-throughput 
screen can be developed with the target?  Has the applicant designed an 
appropriate set of experiments to demonstrate a critical site of vulnerability 
in the cancer cell which can exploited for treatment or prevention?  If crude 
natural product extracts are proposed, are strategies for compound isolation 
and identification adequate?  If structural biology studies are proposed, are 
plans adequate for the production of materials and have appropriate 
collaborations been arranged?  If screening is proposed, are data handling 
procedures adequate, and is the assay validated and appropriate for large-
scale or high throughput use?

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?  Will the approaches advance the use 
of new, validated molecular targets for new drug discovery?

Investigator:  Is the investigator appropriately trained and suited to carry 
out the project?  Is the research proposed appropriate to the experience level 
of the PI and other researchers (if any)?

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 valuable 
collaborative arrangements?

Additional Considerations

The initial review group will also examine: the appropriateness of the 
proposed 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 of human 
and animal subjects; and the safety of the research environment.

Applications recommended by the National Cancer Advisory Board will be 
considered for award based upon (a) scientific and technical merit; (b) 
program balance, including in this instance, sufficient compatibility of 
features to make a successful collaborative program a reasonable likelihood; 
and (c)  availability of funds. 

Written and telephone inquiries concerning this PA are encouraged.  The 
opportunity to clarify  any issues or questions from potential applicants is 
Direct inquiries regarding programmatic issues in cancer treatment, to the 
appropriate individuals given in the GCOB web site:  
(On the panel, left side, click on "Funding", then scroll down to "Staff").  
Inquiries regarding access to the Natural Products Repository and inquiries 
regarding access to the Synthetic Compound Repository of NCI refer to the 
appropriate paragraph in the SPECIAL REQUIREMENTS section.

Direct inquiries regarding programmatic issues in cancer prevention to the DCP 
web site:	

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
Bethesda, MD  20892-8239
Rockville, MD  20852 (for express/courier service)
Telephone (301) 496-3428
Fax: (301) 402-0275
Direct inquiries regarding fiscal matters to: 
Ms. Kathleen Shino
Grants Administration Branch 
National Cancer Institute 
Executive Plaza South 243 				
Bethesda, MD  20892-7150
Telephone:  (301) 496-8635 
Fax: (301) 496-8601
This program is described in the Catalog of Federal Domestic Assistance No. 
93.395, Cancer Treatment Research.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act, as amended, (42 USC 241 
and 284) and administered under NIH grants policies and Federal Regulations 42 
CFR 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 PHS strongly encourages all grant and contract 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.  

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