IN THIS ISSUE
Breathalyzing for cancer – page 3
2 Message from the Director
3Discoveries
3Updates
Science at the heart of medicine
4 Our Supporters
NEWS
Einstein Cancer Center
From Atoms
to Animals to
Patients with
Cancer
Newsletter of the
Albert Einstein Cancer Center
I S S U E 4 • S U M M E R / FA L L 2 0 1 1
P
ut an immuno-oncologist, a molecular immunologist and an X-ray
crystallographer in one room and you may get a new approach to
cancer treatment.
More than 90 percent of cancer deaths are caused not by the primary tumor but
rather by the cancer’s spread, known as metastasis. “Surgery, chemotherapy and
radiation can often control primary cancer growth, but successful control of metastatic cancer remains rare,” says immuno-oncologist Xingxing Zang, Ph.D., assistant professor of microbiology & immunology. Einstein researchers are working on
a new approach to treating cancer metastases: activating the immune system.
“The basis of immunotherapy for cancer is that the immune system’s T cells
can recognize foreign antigens on tumors and reject the tumors,” says molecular
immunologist Stanley G. Nathenson, M.D., Distinguished Professor in the departments of microbiology & immunology and of cell biology and the Samuel H.
Golding Chair in Microbiology.
Existing cancer therapies such as interferon and interleukin 2 help encourage
the immune system to attack tumors, but the heightened immune response is
Above, Steven C. Almo, Ph.D., left, confers with Xingxing Zang, Ph.D., and
Stanley G. Nathenson, M.D. Their collaborative relationship benefits from their
differing areas of expertise.
(continued on page 2)
MESSAGE FROM
THE DIRECTOR
I. DAVID GOLDMAN, M.D.
Director, Albert Einstein
Cancer Center
Professor, Departments of
Medicine and
Molecular Pharmacology
Susan Resnick Fisher
Professor
S
ince the start of the 20th
century, scientists have
sought ways of harnessing the immune system to attack
cancer cells. The challenge has
been enormous. The immune
system is designed to destroy
foreign elements such as bacteria
and viruses. Cancer cells are not
sufficiently different from their
normal counterparts to elicit an
immune response; when there
are differences, the cancer cells
“learn” ways to block an immune
response. So the goal is to teach
the immune system to attack the
cancer without attacking normal
tissues.
This issue of the newsletter
describes a novel immunological
approach being developed at the
Albert Einstein Cancer Center by a
group of collaborating scientists,
based on a recent exciting finding: the identification of a protein
molecule on cancer cells, B7x, that
blocks the normal functions of
immune cells, thereby protecting
cancer cells from immune attack.
What makes this approach particularly promising is that B7x is
present on many different human
cancers but apparently not on
normal human tissues. When an
antibody, for example, blocks B7x
in a tumor-bearing mouse, there is
an antitumor effect but little or no
damage to normal tissues. These
studies by Einstein scientists are a
promising step toward achieving
what has been an elusive goal in
cancer immunotherapy.
From Atoms to Animals to Patients with Cancer (continued from page 1)
usually not cancer specific, and it can
cause severe autoimmune disease. So
the Einstein researchers are examining
the interaction between cancer cells
and T cells to learn how to fine-tune
and boost immunity to work against
cancer.
When a T cell encounters a cancer
cell, receptor proteins on the T cell’s
surface bind to proteins on the cancer
cell’s surface. These connections
between the T cell and the cancer cell
are crucial: Some prompt T cells to go
into attack mode, while others turn T
cells off, explains Dr. Nathenson.
The Einstein team is looking closely
at B7 proteins—a family of proteins
on the surface of tumor cells that
inhibit T cells from attacking cancer
cells. Determining the structure of
the molecular complex formed when
the B7 proteins lock with their binding sites on T cells is the job of X-ray
crystallographer Steven C. Almo,
Ph.D., professor of biochemistry and
of physiology & biophysics.
Dr. Zang is especially interested
in a newly discovered member of the
B7 family called B7x. He and his colleagues found that expression of B7x
on tumor cells accelerated cancer progression in mice. In addition, cancer
often spreads in men whose prostate
tumors produce an overabundance of
B7x, making cancer recurrence and
death more likely. B7x also appears
to play a role in cancers of many
other organs such as the lung, ovary,
breast, uterus and pancreas. After Dr.
Almo and his team develop crystals
In this microscope image (magnification
x60) from Dr. Zang’s lab, red areas are
human ovarian tumor cells overexpressing
the cancer-promoting protein B7x.
of B7x, the researchers can observe
how the crystal bends an X-ray beam
(its diffraction pattern), revealing the
protein’s complex shape and providing clues to its function.
“Our aim is to put the B7 proteins—and B7x in particular—out of
action so that an immune response
against cancer cells can occur,” says
Dr. Zang. With the help of Dr. Almo’s
X-ray crystallography images, Dr.
Zang is designing small molecules
that bind to and block B7x and the
other B7 proteins on the surface of
tumor cells. Dr. Zang has already
developed mouse monoclonal antibodies (antibodies that are identical
because they are made by immune
cells cloned from a unique parent
cell) that inactivate B7x. When these
antibodies are converted to human
forms they will be ready for evaluation
in clinical trials.
ON THE WEB
Dr. Nathenson’s lab: www.einstein.yu.edu/cellbiology/nathenson.htm
Dr. Zang’s lab: www.einstein.yu.edu/zang
Dr. Almo’s Structural Biology/X-Ray Crystallography Facility:
www.einstein.yu.edu/sr/xraycrystal
CANCER Q&A
Q: Can I strengthen my immune system to fight cancer?
A: The risk of cancer increases when the immune system is weak—as in AIDS, for
example, or when a person’s immune system is purposely suppressed to prevent
rejection of a transplanted organ. But there is no evidence that strengthening a
normal immune system can reduce cancer risk. You may have seen ads claiming
that certain foods, herbs or other dietary supplements can boost your immune
system, and some studies suggest that regular exercise may rev up the immune
system. But no one has yet shown that foods, supplements or exercise can bolster
immune function sufficiently to fight cancer.
discoveries
Blocking a Metastasis Booster
A Stem Cell Shield Against Radiation
Breathalyzing for Cancer
What molecules contribute to the deadly
process of cancer
spread known as
metastasis? Working with mice, Anne
R. Bresnick, Ph.D.,
professor of biochemistry, and her
colleagues have identified and determined the function of S100A4, a protein found in elevated concentrations
in several metastatic cancers.
High levels of S100A4 are synthesized by macrophages—immune
cells that normally roam the body
and attack disease-causing microbes.
S100A4 controls the movement of
macrophages and may promote
metastasis by recruiting macrophages
to the primary tumor. Macrophages
contribute to metastasis by helping
cancer cells escape the primary tumor
and invade blood vessels, which
transport the cancer cells to distant
sites. Identifying S100A4’s key role in
metastasis could lead to drugs that
block cancer spread by targeting this
protein. The team reported its findings in a 2010 issue of Molecular
Biology of the Cell.
Radiation—whether
from cancer therapy
or from a dangerous
dirty bomb—can prove
fatal if it damages the
sensitive lining of the
intestines. Chandan
Guha, M.B.B.S., Ph.D., professor of
radiation oncology and of pathology
and vice chair of the department of
radiation oncology, has shown that
mice can survive a lethal dose of
radiation if they receive transplanted
stromal stem cells from the bone marrow of other mice within 24 hours of
radiation exposure. The Centers for
Medical Countermeasures Against
Radiation (funded by the National
Institutes of Health) has awarded Dr.
Guha a five-year, $11.8 million grant
to continue his research on these stem
cell transplants, which could save the
lives of victims of radiation overexposure. The techniques that Dr. Guha
is developing could also be applied
to minimize toxicity in patients with
abdominal cancers treated therapeutically with ionizing radiation.
Simon D. Spivack,
M.D., M.P.H., professor of medicine
(pulmonary medicine),
of epidemiology &
population health and
of genetics, is working
to detect lung cancer at the earliest
possible time—when prospects for
treatment success are highest. Using
a technique he developed, Dr. Spivack analyzes DNA and other nucleic
acids recovered from cells in exhaled
breath. If the DNA contains abnormally high numbers of methyl groups
(chemicals known to be involved in
turning genes off), that’s a sign that
cells of the lung or other parts of the
airway are being transformed into
cancer cells. This noninvasive technique could lead to a valuable test for
detecting early-stage lung cancer.
ON THE WEB
To learn more about the Albert
Einstein Cancer Center, please
visit www.einstein.yu.edu/cancer.
updates
New Faculty
The Albert Einstein
Cancer Center
welcomes Eleni
Andreopoulou, M.D.,
assistant professor
in the department of
medicine (medical oncology). She was previously a faculty
member in the department of breast
medical oncology at the University of
Texas M. D. Anderson Cancer Center.
Dr. Andreopoulou completed her
clinical and research training at St.
Bartholomew’s Hospital and the Royal
Marsden Hospital/Institute of Cancer
Research in London, and at New York
Congratulations!
University School of Medicine. Her
academic interests include metastatic
and locally advanced breast cancer,
neoadjuvant drugs (tumor-shrinking
drugs that are given prior to surgery)
and assessing the genes expressed in
tumors to help physicians choose the
best drugs for particular patients. Her
research focuses on bringing moreeffective drugs into the clinic and
developing innovative designs for
clinical trials that will lead to better
outcomes for patients with breast
cancer. She is the principal investigator for a number of clinical trials and
also has an active clinical practice.
The American Association for Cancer Research has awarded Susan
Band Horwitz, Ph.D., Distinguished
Professor and co-chair of the department of molecular pharmacology
and the Rose C. Falkenstein Chair in
Cancer Research, its eighth Award
for Lifetime Achievement in Cancer
Research. Dr. Horwitz was honored
for her pioneering research establishing the mechanism of action of the
cancer chemotherapeutic drug Taxol
(paclitaxel). Taxol has been used by
more than one million patients worldwide to treat cancers of the ovary,
breast and lung.
our supporters
NOTABLE GIFTS AND GRANTS
The Albert Einstein Cancer Center (AECC) gratefully acknowledges the generosity of the following donors, whose support
is critical to advancing its mission.
The Estate of Beatrice Steinhauser recently made a bequest to Einstein of approximately $689,000. In accordance with
Mrs. Steinhauser’s wishes, part of the gift
has been designated for cancer research.
The funds will help support Einstein’s new
shRNA genomics facility. Established with
the support of Einstein Overseer Arthur
Hershaft and his wife, Janet Hershaft,
the facility offers investigators a technology for probing the genetic origins of
cancer and autoimmune disorders.
The Irma T. Hirschl Trust, a longtime
generous supporter of medical research
at Einstein, has awarded a $175,000
grant to Antonio Di Cristofano, Ph.D.,
associate professor of developmental
and molecular biology and of obstetrics
& gynecology and women’s health, for
his investigation into genetically altered
tumor cells in mice that are sensitive to
drugs that inhibit glycolysis (the breakdown of glucose by enzymes to release
energy). Dr. Di Cristofano’s research is
directed toward developing drugs to
disrupt this pathway in cancer cells.
To learn more about supporting the work
of the AECC, please contact:
IRA LIPSON
Director of Institutional Advancement
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue, Mazer 725
Bronx, NY 10461
718.430.2371, ira.lipson@einstein.yu.edu
EVENTS
Einstein’s Cancer Research Advisory
Board hosts events during the year that
bring together people interested in supporting the work of the Albert Einstein
Cancer Center with distinguished
Einstein faculty members who share the
latest developments in cancer research.
Last March in Florida, three special events
were held for friends and supporters
of the College of Medicine: Einstein
Overseers Marilyn and Stanley M. Katz
hosted a luncheon at the Palm Beach
Country Club; Einstein Overseers Karen
Mandelbaum and Sue-ann Friedman cohosted a reception at Ms. Mandelbaum’s
home in Jupiter; and Helen and Ronald
Ross, M.D. ’60, hosted a reception at the
Polo Club Boca Raton.
The events were part of “Einstein in
Florida 2011,” a series of presentations
by leading faculty members highlighting
some of the latest research developments
at Einstein. Steven K. Libutti, M.D.,
professor of surgery and of genetics, vice
chair of the department of surgery and
ALBERT EINSTEIN
CANCER CENTER
Our mission: to promote and conduct
research that will elucidate the origins
of cancer and lead to effective new
approaches for the prevention, diagnosis
and treatment of malignant diseases
From left: Joseph Sparano, M.D., Mary
Jane Happy, Emily Miller and Dean Allen M.
Spiegel at the Einstein Women’s Division’s
2011 Spirit of Achievement Luncheon.
associate director of clinical services
at the AECC, was a guest speaker
along with Allen M. Spiegel, M.D., the
Marilyn and Stanley M. Katz Dean, and
Robert E. Michler, M.D., professor and
chair, departments of surgery and of
cardiovascular and thoracic surgery.
Dr. Libutti’s research into new targeted
cancer treatments is supported in part by
a generous gift from Einstein Overseer
Linda Altman and her husband, Earle
Altman.
ADMINISTRATION
Director
I. David Goldman, M.D.
Deputy Director
Jeffrey Pollard, Ph.D.
Joseph A. Sparano, M.D., professor of
medicine and of obstetrics & gynecology
and women’s health and director of the
breast cancer program and clinical trials
office of the AECC, was honored by the
Einstein National Women’s Division at
its 57th Annual Spirit of Achievement
Luncheon at the Plaza Hotel on May 5.
Proceeds will benefit the division’s $3
million initiative to support research on
women’s cancers at the AECC.
Joining Dean Spiegel in presenting
the 2011 Spirit of Achievement award
to Dr. Sparano were Mary Jane Happy, a
patient of Dr. Sparano, and her daughter,
Emily Miller, an M.D./Ph.D. candidate at
Einstein. In addition to 350-plus members
and friends of the Women’s Division,
the attendees included AECC Director I.
David Goldman, M.D.; AECC Associate
Director Susan Band Horwitz, Ph.D., a
past Spirit Awardee; and AECC Associate
Director Roman Perez-Soler, M.D.
Associate Directors
Leonard Augenlicht, Ph.D.
Susan Horwitz, Ph.D.
Steven Libutti, M.D.
Roman Perez-Soler, M.D.
Michael Prystowsky, M.D., Ph.D.
Thomas Rohan, M.D., Ph.D.
Richard Seither, Ph.D., M.S., M.B.A.
Pamela Stanley, Ph.D.
ADVISORY BOARD
Chairperson
Marilyn R. Katz