Issue #3, January 2008
Editor, Ron Bose, M.D., Ph.D.
Table of Contents
-Meeting Notes: AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference -AACR Funding
Opportunities – $3 Million in New Grants Available -CICR Election: Please Vote! -Announcing: Recipient of
AACR Chemistry Award -AACR Annual Meeting 2008 -Young Chemists’ Committee: Volunteers Needed -Travel
Awards Available -CICR Membership
EDITOR’S NOTE
--Ron Bose, M.D., Ph.D.
This issue of the newsletter features a summary of the AACR-NCI-EORTC Molecular
Targets and Cancer Therapeutics Conference and provides information about some
of the CICR working group events at the upcoming AACR Annual meeting in April.
We look forward to seeing many of you there. This issue also includes commentaries
from the Young Chemists’ Committee (YCC) of the CICR. The YCC also seeks senior
scientists to volunteer at networking sessions with young investigators.
In keeping with the current Presidential primaries, the CICR is
holding its own election process starting mid January and we encourage all CICR
members to vote.
This newsletter is published quarterly and contributions from any AACR member
are welcome. Comments, submissions, or questions should be directed to me
at rbose@im.wustl.edu and to Eileen Dougherty, our AACR Program
Coordinator, at eileen.dougherty@aacr.org.
MEETING NOTES
AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference
--Randy Wadkins, Ph.D and Kathlynn Brown, Ph.D.
The 2007 AACR-NCI-EORTC International Conference on Molecular Targets and
Cancer Therapeutics took place October 22-26 at the Moscone West Convention
Center in San Francisco. The meeting consisted of plenary sessions in the morning
with concurrent sessions in the afternoon. Topics ranged from personalized cancer
therapies to emerging kinase targets. In past years, this meeting has been an excellent gathering spot for
chemists interested in development of novel anti-cancer drugs. This year, the meeting was more focused on
target discovery, with many chemists' presentations occurring during the poster sessions. Three poster sessions
were held in which almost 900 posters
were presented.
There may be an obvious reason this meeting emphasizes new target discovery. John Heymach of the
M.D. Anderson Cancer Center, in his presentation of results with angiogenesis inhibitors to treat non-small cell
lung cancer, noted that a recent review of the NCI's SEER data from the last 22 years of research and
development in treatment of this disease had concluded that the average time from diagnosis to death
increased by only 12 days. Other cancers haven't fared much better. Consequently, for synthetic chemists to
truly move forward, identification of novel targets is critical. As Nicholas C. Dracopoli of Bristol-Myers Squibb
noted, R&D costs continue to rise while FDA approval of new anti-tumor drugs has decreased significantly from
prior years.
Even when a target is identified and small molecules that affect the target are
developed in vitro, there's no guarantee that these are effective clinically. Steven D.
Gore of the Johns Hopkins University School of Medicine has been at the forefront of
clinical testing of 5 azacytidine as an inhibitor of DNA methyltransferase and sodium
phenylbutyrate as an inhibitor of histone deacetylase. In sequential combinations of
5
azacytidine followed by sodium phenylbutyrate, correlative studies showed
demethylation of p15 promoter in clinical responders but not in non-responders.
However, in the subsequent study of 5-azacytidine with the oral histone deacetylase inhibitor MS-275 (now
SNDX-275), methylation reversal did not appear to correlate with clinical response. Hence, his
presentation was appropriately titled "Epigenetic Therapies: What is the Target?"
Other highlights of the meeting of potential interest to chemists studying cancer biology are discussed
below.
Peter B. Dirks presented his work in the “Cancer Stem Cell” plenary session. Using neurosphere
proliferation as an assay for neural stem cell self-renewal, his laboratory screened a small molecule library to
identify inhibitors of this process. In addition to identifying cytotoxic compounds, drugs known to have an effect
on neural transmission were identified. Compounds were identified which exhibit their effects on neurospheres
but not on astrocytes, indicating specificity for the neuronal stem cell population. Interestingly, some of the
small molecule hits may have selectivity for cancer stem cells compared to normal neuronal stem cells. In the
same session, Craig T. Jordan described a parthenolide analog, dimethylamino-parthenolide which causes cell
death in leukemia stem cells and the bulk leukemic cells but does not affect their healthy counterparts. This
agent has improved pharmacodynamic parameters when compared to the parental compound.
During the session “Small Molecule Approaches to the Regulation of Apoptosis” Gregory Verdine
presented work that uses peptides to regulate protein-protein interactions. His laboratory has taken advantage
of ruthenium catalyzed olefin metathesis to “staple” peptides from the BID domain of BCL-2 proteins, thus
locking these peptides into an alpha-helical structure. This results in peptides that can disrupt the native
protein complex, inducing apoptosis. His laboratory has made the stapled peptide versions of the BID3
domains of the BCL-2 family members. These peptides are cell permeable, promote apoptosis, and retain their
differential binding, and they are now moving into clinical testing.
The session “High Throughput Screen for Target Identification” focused on genetic screens. Michael
White presented data from a genome wide siRNA screen that was employed to determine genes that sensitize
cancer cells to a non-lethal dose of a chemotherapeutic. This approach is expected to aid in the rational design
of therapeutic drug combinations. Angelique Whitehurst, a postdoctoral fellow in Dr. White’s laboratory, was
awarded the AACR-WICR Brigid G. Leventhal Scholar Award in Cancer Research. She presented a poster in the
Target Identification and Validation session entitled “Revealing targets for combinatorial chemotherapy using
genome-wide RNAi” in which she identified the CT-antigen, ACRBP, as a gene whose depletion sensitizes lung
cancer cells to paclitaxel.
The 2008 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics will take
place October 21-24 in Geneva, Switzerland.
Webcasts from the conference are now available on the AACR website.
AACR FUNDING OPPORTUNITIES – $3 MILLION IN NEW GRANTS AVAILABLE
Major Grants
LANDON FOUNDATION-AACR INNOVATOR AWARD FOR INTERNATIONAL COLLABORATION
Application deadline: February 15, 2008
The Award provides a two-year, $100,000 institutional grant to support an established international cancer
research collaboration. For more information, complete eligibility requirements and award terms, visit the
AACR website.
THE JEANNIK M. LITTLEFIELD-AACR GRANTS IN METASTATIC COLON CANCER RESEARCH
Application deadline: February 15, 2008
Provides $500,000 -$1,000,000 to independent investigators; the AACR will award 2-4 grants in 2008.
For more information, complete eligibility requirements and award terms, visit the AACR website.
Grants for Junior Faculty
AACR-GENENTECH BIOONCOLOGY CAREER DEVELOPMENT AWARD FOR CANCER RESEARCH ON THE HER
FAMILY PATHWAY – two-year grant of $100,000; applicants must hold an M.D. or M.D./Ph.D.
LANDON FOUNDATION-AACR INNOVATOR AWARD FOR CANCER PREVENTION RESEARCH
Application Deadline: February 15, 2008
A two-year grant of $100,000 ($50,000 per year) will be provided to the recipient’s institution to support direct
research expenses; salary and benefits; and attendance at the AACR Annual Meeting, Cancer Prevention
Conference, or other AACR meeting relevant to cancer prevention for the purpose of participating in scholarly
exchange.
For more information, complete eligibility requirements and award terms, visit the AACR website.
Grants for Pre-and Postdoctoral Fellows
Application deadline: February 1, 2008 Visit the AACR website for more information.
AACR Centennial Pre-doctoral Research Fellowships in Cancer *NEW GRANT* – $30,000 per year over a
maximum period of three years will be awarded for salary support and research funding.
AACR Centennial Postdoctoral Research Fellowships in Cancer Research *NEW GRANT* – $60,000 per year
for up to three years; provides salary support and research funding.
AACR-AstraZeneca-Prevent Cancer Foundation Fellowship for Translational Lung Cancer Research –
three-year grant of $90,000.
AACR-Pancreatic Cancer Action Network Fellowship for Pancreatic Cancer Research, in memory of Samuel
Stroum – one-year grant of $45,000; US institutions only.
AACR-Genentech BioOncology Fellowship for Cancer Research in Angiogenesis – two-year fellowship of
$70,000; applicants must hold an M.D. or M.D./Ph.D.
AACR-Colorectal Cancer Coalition Fellows Grant, in memory of Lisa Dubow – one-year grant of $30,000.
AACR-FNAB Foundation Fellows Grant for Translational Pancreatic Cancer Research – one-year grant of
$35,000.
CHEMISTRY IN CANCER RESEARCH ELECTION FOR CHAIRPERSON-ELECT OF STEERING
COMMITTEE
Voting will take place from January 18 to February 1, 2008 for Chairperson-Elect of the CICR Steering
Committee. Laurence H. Hurley, D.Sc., Ph.D. and Larry K. Keefer, Ph.D. are standing for election. Information
about these candidates, a ballot can be found on the AACR website. Members may send votes to cicr@aacr.org.
AACR ANNUAL MEETING 2008
AACR AWARD FOR OUTSTANDING ACHIEVEMENT IN CHEMISTRY IN CANCER RESEARCH
rd
Dr. Steven R. Tannenbaum has been awarded the 3 Annual AACR-CICR Award in recognition of his seminal
contributions to advances in our knowledge of chemical carcinogenesis, molecular epidemiology of cancer and,
more recently, anticancer drug development and evaluation.
Dr. Tannenbaum will be presented with the Award and give the lecture on Sunday, April 13, 2008, from
5:30 p.m.-6:30 p.m., during the AACR Annual Meeting in San Diego, CA. CICR TOWN MEETING AND
RECEPTION CICR will host a Town Meeting and Reception open to all Annual Meeting attendees interested in
Chemistry in Cancer Research on Sunday, April 13, 2008 from 6:45 p.m.-8:30 p.m. at
the Omni Hotel.
YOUNG CHEMISTS’ COMMITTEE
MESSAGE FROM THE CHAIRPERSON Amanda Bryant-Friedrich, Ph.D.
The Young Chemists’ Committee (YCC) of the Chemistry in Cancer Research Working
Group wishes all members a happy and productive 2008. The Committee is poised to
make significant contributions to the AACR through its activities within CICR, using programs
and initiatives targeted at the young chemists considering, involved in or collaborating with
those in a cancer-centered research program. In order to ensure that this group of
investigators has the collective voice needed to make their concerns known, the Committee
has expanded its membership to thirteen scientists representing researchers from industrial,
academic and government entities. Our members include
those currently pursing graduate degrees, fulfilling postdoctoral commitments and those early in their faculty
and industrial careers. The YCC seeks to serve those not just young in age, but also individuals new to the
world of cancer research.
VOLUNTEERS NEEDED One of the primary areas of need that the committee has identified is the recruitment
and engagement of seasoned mentors for those who need guidance in various areas of cancer research. During
the 2007 Molecular Targets meeting, a Mentoring Roundtable Session was introduced which proved to be very
popular among the target audience of the YCC. We hope to continue this concept at the 2008 AACR Annual
Meeting and possibly the upcoming 2008 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics. To assist in this effort, the Committee invites all senior chemists who have an interest in
interacting with newcomers in the field of chemistry to volunteer at these upcoming sessions. The benefits to
the mentees are obvious, but there are also value benefits for the mentors as well. If you are not chemists in
this field, you may acquire knowledge from those using cutting-edge chemistry techniques in your area of
interest. The wide eye naiveté of a young scientist may also bring a fresh look to old problems in your
laboratory that can enliven your studies. I encourage those who have reaped the benefits of a dedicated mentor
or who have a general interest in this theme to contact Ms. Eileen K. Dougherty of the AACR to express your
interest in this exciting opportunity.
ACADEMIC FUNDING WOES: PERSPECTIVE OF THE CICR YOUNG CHEMISTS’ COMMITTEE Erin
Prestwich, Ph.D. and Amanda Bryant-Friedrich, Ph.D.
Concerns surrounding the planning and execution of a successful career are foremost in the
minds of many members of the CICR Younger Chemists’ Committee (YCC). Many
of the youngest scientists of the committee are currently weighing the pros and
cons of choosing an academic or industrial career in science or whether to venture
out into other fields. Conversations frequently focus on the desire to remain in
academia, but the uncertainty of procuring funding has surfaced as a major
deterrent. This is understandable, as NIH funding levels for competing grants
hovered at 21.3% for 2007, while the average age for Ph.D.s to receive their first
RO1 has crept linearly to 41.7 in 2004 from 34 in 1970. The outlook for 2008
appears grim with NIH funding increasing only by 1.1%, a level much below
inflation. As younger chemists, it often seems we are powerless to change the
funding situation in academia, but we have options other than avoidance of
academia altogether. We can lobby those in government as well as those in powerful organizations such as
AACR for more awards to new investigators and also support politicians who are committed to increasing
funding of basic science. A combined voice from those interested in the advancement of young scientists in
relevant fields of research, such as cancer research, can make organizations like the YCC have a major impact
on the future of research in the academy.
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TRAVEL AWARDS AVAILABLE FOR AACR CONFERENCES
Scholar-in-Training Awards will be awarded to highly-rated abstracts by early-career scientists, and
Leventhal Scholar Awards will be awarded to highly-rated abstracts by early-career scientists who are members
of Women in Cancer Research (WICR).
Minority Scholar Awards and Minority-Serving Institution Faculty Scholar Awards are available to eligible
attendees through an application process.
See the AACR website for more information on these conferences, including programs, schedules, and
award criteria.
CICR MEMBERSHIP
The AACR will automatically renew your membership to the CICR Working Group unless you inform the AACR
that you no longer wish to be a member. Questions about CICR membership may be sent to cicr@aacr.org.
Please visit the CICR website. To be removed from this list please e-mail Program Coordinator Eileen K.
Dougherty at eileen.dougherty@aacr.org. Click here to update your e-mail address or contact information. Click
here if you forgot your account ID and password for eServices.
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NIH Mervis, J., Science, 2008, 319, 18-19.