Full Text PA-97-086
 
CHEMICAL MODIFIERS OF RADIATION RESPONSE OF TUMORS
 
NIH GUIDE, Volume 26, Number 24, July 25, 1997
 
PA NUMBER:  PA-97-086
 
P.T.


Keywords: 

 
National Cancer Institute
 
PURPOSE
 
The Division of Cancer Treatment, Diagnosis, and Centers (DCTDC) of
the National Cancer Institute (NCI) invites research grant
applications for Program Projects (P01s) from interested
investigators for preclinical exploration of the therapeutic
potential of new and novel chemical modifiers of radiation response
of tumors. Optimization of leads arising from the applicant's own
work or from the published literature should include the design and
synthesis of new compounds, using combinatorial chemistry, and
preclinical evaluation in vitro and in vivo.
 
The following classes of radiation modifiers are of particular
interest:
 
o Small-molecule inhibitors that target genetic alterations
associated with solid tumors
o Small-molecule modifiers of cell growth and regulation (modifiers
of cell cycle checkpoints, cell signal transduction modifiers)
o Compounds that exploit or modulate tumor physiology (e.g.,
inhibitors of tumor cell respiration, modulators of the tumor micro
environment, or inhibitors of tumor angiogenesis)
o Prodrugs activated by tumor physiology or by other innovative
mechanisms
 
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 PA,
"Chemical Modifiers of Radiation Response of Tumors" 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
"Healthy People 2000" (Summary Report: Stock No. 017-001-0473-1)
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. Foreign applicants are
not eligible. Racial/ethnic minority individuals, women, and persons
with disabilities are encouraged to apply as principal investigators.
 
MECHANISM OF SUPPORT
 
Support of the program will be through the National Cancer Institute
(NCI) program project (P01) award. Applicants will be responsible for
the planning, direction, and execution of the proposed project. All
PHS and NIH grants policies will apply to applications received and
awards made in response to this program announcement. The Principal
Investigator of any new application requesting $500,000 or more in
direct costs in any one year must notify the NCI Program Director
(see INQUIRIES section) and the NCI Referral Officer (see APPLICATION
PROCEDURES section) of intent to submit an application.
 
RESEARCH OBJECTIVES
 
Background
 
About 60% of cancer patients in the US receive radiotherapy with
curative or palliative intent. About 30% of the patients with
localized disease eventually succumb to the disease, and would stand
to benefit from improvements in radiotherapy. The factors
contributing to local failure of radiotherapy are the subject of
numerous studies, and include inherent radioresistance of tumor
cells, tumor hypoxia, and defects in signal transduction mechanisms
and cell cycle checkpoints. The purpose of this PA is to discover and
develop new agents with  clinical potential for enhancing the
radiation response of tumors, from leads arising out of basic
research.
 
Research Goals and Scope
 
Applicants should propose to discover and develop novel compounds
that act through mechanisms that target cellular or tumor properties
known to affect radiation response, in particular those emerging from
current basic research. The ultimate goal is to improve local tumor
control and survival of cancer patients treated with radiotherapy.
This multidisciplinary effort will require close collaboration among
radiation biologists, chemists skilled in design and synthesis of
organic compounds, and pharmacologists. Projects involving design and
synthesis of novel compounds, determination of physicochemical
properties, evaluation in cultured cells in vitro with and without
ionizing radiation, and evaluation in vivo in animal models,
including confirmation of proposed mechanism of action, would be
appropriate. The new compounds generated may represent a de novo
collection of novel structures or efforts to optimize lead structures
with promising but incompletely studied potential. In no case should
the compounds to be studied be iterations of well-studied structural
classes.
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (REV. 5/95) is to be used
in applying for these grants. These forms 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, Room 6095, MSC
7910, Bethesda, MD 20892, telephone 301/435-0714, e-mail:
asknih@odrockmi.od.nih.gov.
 
Applicants must use the NCI Program Project Guidelines when preparing
an application. These guidelines are available on the World Wide Web
at: http://156.40.252.246/awards/P01.htm or on the NCI Home Page at:
 
http://www.nci.nih.gov/extra/deaweb/dea.htm
 
Copies of the NCI P01 Guidelines can also be obtained from the NCI
Referral Officer listed below:
 
REFERRAL OFFICER
DIVISION OF EXTRAMURAL ACTIVITIES
NATIONAL CANCER INSTITUTE
EXECUTIVE PLAZA NORTH, ROOM 636A
6130 EXECUTIVE BOULEVARD MSC 7405
BETHESDA, MD 20892-7405
TELEPHONE: 301-496-3428
FAX: 301-402-0275
E-MAIL: FRIEDBET@DEA.NCI.NIH.GOV
 
The completed original application and three legible copies must be
sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040-MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
 
In addition, send two complete copies under separate cover to:
 
REFERRAL OFFICER
DIVISION OF EXTRAMURAL ACTIVITIES
NATIONAL CANCER INSTITUTE
EXECUTIVE PLAZA NORTH, ROOM 636A
6130 EXECUTIVE BOULEVARD MSC 7405
BETHESDA, MD 20892-7405
 
Applications will be assigned on the basis of established PHS
referral guidelines. Applications that are complete and responsive to
the program announcement will be evaluated for scientific and
technical merit by an appropriate peer review group convened by
DEA, NCI in accordance with the standard NIH peer review
procedures, and receive a second level review by the National
Cancer Advisory Board.
 
REVIEW CRITERIA
 
Reviewers will be instructed to (a) address the five review criteria
below and (b) assign a single, global score for each scored
application.  The score should reflect the overall impact that the
project could have on the field based on consideration of the five
criteria, with the emphasis on each criterion varying from one
application to another, depending on the nature of the application
and its relative strengths.
 
The goals of NIH-supported research are to advance our understanding
of biological systems, improve the control of disease, and enhance
health.  In the written comments reviewers will be asked to discuss
the following aspects of the application 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 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 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?
 
(3) Innovation:  Does the project employ novel concepts,
approaches or method? 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?
 
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
 
o  The adequacy of plans to include both genders, minorities, and
their subgroups as appropriate for the scientific goals of the
research.  Plans for the recruitment and retention of subjects will
also be evaluated.
 
o  The reasonableness of the proposed budget and duration in
relation to the proposed research
 
o  The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the
project proposed in the application.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
approved applications assigned to the NCI. The following will be
considered in making funding decisions: Quality of the proposed
project as determined by peer review, responsiveness to the goals and
objectives of this Program Announcement, availability of
funds, and program balance.
 
INQUIRIES
 
Inquiries are encouraged. The opportunity to clarify any issues or
questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic matters to:
 
Helen B. Stone, Ph.D.
Division of Cancer Treatment, Diagnosis, and Centers
National Cancer Institute
EPN 800
6130 Executive Blvd.
Bethesda, MD 20892-7440
Telephone: (301) 496-9360
Fax: (301) 480-5785
E-mail: stoneh@dtpepn.nci.nih.gov
 
Direct inquires regarding NCI P01 review policy and procedures
to:
 
David Irwin, Ph.D.
Chief, Research Programs Review Section
Grants Review Branch
Division of Extramural Activities
Executive Plaza North, Room 635E
6130 Executive Boulevard MSC 7405
Bethesda, MD 20892-7405
Telephone: 301-402-0371
Fax: 301-496-6497
E-mail: IrwinD@DEA.NCI.NIH.GOV
 
Direct inquiries regarding fiscal matters to:
 
Ms. Victoria Price
Grants Administration Branch
National Cancer Institute
EPS 243
6120 Executive Blvd.
Bethesda, MD 20892-7150
Telephone: (301) 496-7800, ext. 252
Fax: (301) 496-8601
E-mail: pricev@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 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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