Full Text CA-92-18


NIH GUIDE, Volume 21, Number 21, June 5, 1992

RFA:  CA-92-18

P.T. 34

  Biology, Cellular 
  Biology, Molecular 

National Cancer Institute

Letter of Intent Receipt Date:  July 17, 1992
Application Receipt Date:  October 9, 1992


The Cancer Biology Branch of the Division of Cancer Biology, Diagnosis,
and Centers (DCBDC) of the National Cancer Institute (NCI) invites
applications for grants to study the basic tumor biology of ovarian
cancer of epithelial and non-epithelial origin.  Although interest in
research on these malignancies has increased somewhat in the past
several years, there remains a significant lack of understanding about
the underlying factors, both intrinsic (genetic and cellular) and
extrinsic (epigenetic), that contribute to the development of ovarian
cancer.  This initiative is designed to foster the application of
recent advances in molecular and cellular biology, particularly those
that use cells derived from samples of normal and malignant human
tissues or that aid in development and use of animal models, to study
the generation and spread of ovarian malignancies.


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 Request
for Applications (RFA), Contemportary Approaches to Ovarian Cancer
Biology Research, 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. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325, telephone (202)


Research grant applications may be submitted by domestic and foreign
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 from minority individuals and women are encouraged.


Support of this RFA will be by National Institutes of Health (NIH)
individual research grants (R01).

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  The total
project period for applications submitted in response to the present
RFA may not exceed four years.  The anticipated award date will be
August 1, 1993.


Approximately $1,500,000 in total costs per year for four years will be
committed to fund applications submitted in response to this.  It is
anticipated that eight to ten awards will be made.  This level of
support is dependent on the receipt of a sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plans of the NCI, awards pursuant to this
are contingent upon the availability of funds for this purpose.


Ovarian cancer is the fourth leading cause of cancer deaths in women.
More than 20,000 new cases of ovarian cancer will be diagnosed this
year.  If detected at an early stage, these malignancies respond well
to therapy.  However, because early detection is difficult, the
malignancies are frequently at an advanced stage when discovered;
consequently, many affected women succumb to the disease.

The Cancer Biology Branch supports a spectrum of basic research on how
cancer cells differ from the normal counterparts and the progression
from early neoplastic changes to greater degrees of malignancy.  These
studies range from investigation of the molecular biology of human or
animal tumor cell behavior to analysis of cells in the context of the
tissue of origin or the tissue in an animal model.  This research may
ultimately help to pinpoint steps in the malignant process at which
therapeutic intervention is possible and to identify markers for
detection, diagnosis, and prognosis.

The base of information about the biology of ovarian cancer is limited,
and few facts about its development, particularly at the early stages,
are known.  To define the areas of research that might be expected to
have the greatest impact on the understanding of this malignancy, a
working group was convened in December, 1991.  The working group
concluded that many advances in molecular and cell biology and in the
development of in vitro and in vivo models for various malignancies are
available to apply to ovarian malignancies.  The group also raised a
number of questions that could be addressed.  For example, in ovarian
tumors are there aberrations in the array of hormonal, autocrine, and
paracrine factors that maintain the integrity and function of normal
ovarian tissues?  What are the early genetic or epigenetic changes in
ovarian cancer, and what are the functional results of these changes?
Are there early, malignancy-associated alterations in normal surface or
adhesive properties of ovarian cells that promote the unusual
dissemination characteristics of the disease?  Is there a defined
pre-malignant or latent state in the formation of ovarian cancer, and,
if so, what factors contribute to malignant progression?  Such
questions are but a few of the possible lines of inquiry that might be
fruitful ones for understanding this disease.

The preliminary observations about ovarian cancer suggest many
intriguing features that are unique to these malignancies. Information
is needed about the intrinsic and extrinsic factors that contribute to
the development of ovarian malignancies.  The potential now exists to
apply the techniques used for study of other solid tumors to ovarian
cancer to begin to establish a foundation of basic knowledge about this
disease.  This RFA is intended to encourage a variety of
investigator-initiated research projects.  It may include
collaborations among basic and clinical scientists, and it likely will
embrace an array of molecular and cellular approaches.  Evidence of the
establishment of reliable cellular systems or relevant models should be
included in the applications.



The following is a statement of NIH and ADAMHA policy regarding the
inclusion of women and minorities in study populations.  Applications
that are responsive to this RFA will, by definition, meet the
requirement for inclusion of women.  The inclusion of minorities must
be addressed in applications submitted responding to this RFA.

NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements are required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis must be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale must be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues must be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information must be included in the form PHS 398 in the Research
Plan, Sections 1-4, AND summarized in Section 5, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., Native
Americans [including American Indians or Alaskan Natives],
Asian/Pacific Islanders, Blacks, Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded. However,
every effort should be made to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and reflected in assigning
the priority score to the application.

All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.


Prospective applicants are asked to submit, by July 17, 1992, a letter
of intent that includes a descriptive title of the proposed research,
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 subsequent applications, the information
that it contains is helpful in planning for the review of applications.
It 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:

Dr. Cheryl L. Marks
Program Director for Molecular Biology
Tumor Biology Program
Division of Cancer Biology, Diagnosis, and Centers
National Cancer Institute
Executive Plaza South, Room 630
Bethesda, MD  20892-9904*
Telephone:  (301) 496-7028
FAX:  (301) 402-1037

*Applicants who use express mail or a courier service are advised to
use the following street address:

Executive Plaza South, Room 630
6120 Executive Blvd.
Rockville, MD  20852


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional business offices and from the Office of Grants Inquiries,
Division of Research Grants, National Institutes of Health, 5333
Westbard Avenue, Room 449, Bethesda, MD  20892-9912, telephone (301)

The RFA label available in the PHS 398 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 number and title, "Contemporary Approaches to Ovarian Cancer
Biology Research," must be typed on line 2a of the face page of the
application form and the YES box must be marked.

Submit a signed, typewritten original of the application, includ- ing
the Checklist, and three signed, exact, clear, single-sided
photocopies, in one package with the appendices to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892-9912**

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

Referral Officer
Review Logistics Branch
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 848
5333 Westbard Avenue
Bethesda, MD  20892-9912*

*Applicants who wish to use express mail or a courier service should
change the zip code to 20816.

Applications must be received by October 9, 1992.  If an application is
received after that date, it will be returned to the applicant without
review.  The Division of Research Grants (DRG) will not accept any
application in response to this announcement that is essentially the
same as one currently pending initial review, unless the applicant
withdraws the pending application.  The DRG 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.


Upon receipt, applications will be reviewed by DRG staff for
completeness.  Incomplete applications will be returned to the
applicant without further consideration.  Complete applications will be
evaluated by NCI program staff to determine responsiveness to the
program requirements and criteria stated in this RFA.  If the
application is not responsive to the RFA, NCI staff will contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.

If the number of applications is large compared to the number of awards
to be made, NCI may conduct a preliminary scientific peer review
(triage) to eliminate those that are clearly not competitive.  The NIH
will withdraw from further competition those applications judged to be
non-competitive for award and notify the applicant Principal
Investigator and institutional official.  Those applications that are
complete and responsive will be evaluated in accordance with the
criteria stated below for scientific and technical merit by an
appropriate peer review group convened by the Division of Extramural
Activities, NCI.  The second level of review by the National Cancer
Advisory Board considers the special needs of the Institute and the
priorities of the National Cancer Program.
The factors considered in evaluating the scientific merit of each
response to this RFA will be:

o  scientific and technical significance and originality of proposed

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal Investigator
and staff;

o  availability of the resources, including reliable in vivo or in
vitro models, necessary to perform the research;

o  appropriateness of the proposed budget and project duration in
relation to the proposed research;


The anticipated date of award is August 1, 1993.  In addition to the
technical merit of the application, the NCI will consider how well the
proposed research meets the goals and objectives of the program as
described in the RFA.


Written and telephone inquiries concerning the objectives and scope of
this RFA and inquiries about whether or not specific proposed research
would be responsive are strongly encouraged and are to be directed to
the program director listed below.  NCI program staff welcome the
opportunity to clarify any issues or questions from potential

Direct inquiries regarding program issues to:

Dr. Cheryl L. Marks
Program Director for Molecular Biology
Tumor Biology Program
Division of Cancer Biology, Diagnosis, and Centers
National Cancer Institute
Executive Plaza South, Room 630
Bethesda, MD  20892
Telephone:  (301) 496-7028
FAX:  (301) 402-1037

Direct inquiries regarding fiscal and administrative matters to:

Mr. Robert Hawkins
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 13


This program is described in the Catalog of Federal Domestic Assistance
No. 93.396, Cancer Biology.  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 52 and 45 CFR
Part 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review.


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