Winter 2015 - Icahn School of Medicine

The Tisch Cancer Institute
WINTER 2015
DIRECTOR’S REPORT
www.icahn.mssm.edu/tisch
Accelerating Science — Advancing Medicine
The Mount Sinai Health System will expand genomic sequencing and analysis
this year, enabling oncologists to analyze a much broader population of cancer
patients with the most up-to-date tools.
This new initiative—under the leadership
of Robert Maki, MD, PhD, FACP, Steven
Ravitch Chair in Pediatric HematologyOncology, and Professor of Medicine,
Pediatrics, and Orthopaedics—represents
Mount Sinai’s first step in developing an
in-depth analysis of each cancer patient.
Our goal is to uncover valuable information
on mutations among key driver genes and
alterations to signaling pathways, which will
lead to effective, individualized treatments.
The Mount Sinai Health System diagnoses
more than 9,000 new cases of cancer
each year. Patients with common tumors
will be tested against a genetic mutation
panel recognized for its ability to predict
treatment outcomes for various types
of cancer. While all cancers will not be
tested initially, most patients with breast,
colon, and lung cancer will be sequenced.
The plan is to steadily grow the panel and
build a sophisticated database of genomic
information.
Genomic sequencing at Mount Sinai will be a
collaborative effort among Dr. Maki’s team of
scientists and those of Carlos Cordon-Cardo,
MD, PhD, Irene Heinz Given and John LaPorte
Given Professor of Pathology, and Chair of
Pathology; Janina Longtine, MD, Vice Chair
of Molecular Pathology and Genetics; and Eric
Schadt, PhD, Jean C. and James W. Crystal
Professor of Genomics, and Director of the
Icahn Institute for Genomics and Multiscale
Biology.
Steven J. Burakoff, MD, Director, The Tisch
Cancer Institute, and the Lillian and Henry M.
Stratton Professor of Cancer Medicine
Together, these groups will quantitatively
analyze and identify associations among
vast amounts of data from genomic testing
and electronic medical records. By examining
DNA alterations in cancer, the gene sequencing
initiative is expected to contribute to better
care and outcomes for cancer patients across
the Mount Sinai Health System.
A New Era for Bone Marrow Transplantation
A world-class research
Using several cutting-edge
program that promises to
proteomic techniques,
transform the treatment
the team discovered three
of graft-versus-host
plasma biomarkers (TNFR1,
disease (GVHD)—a serious
ST2, and Reg3 alpha),
complication of bone marrow
which led to a grading
transplantation in which the
system to calculate patient
donor’s immune cells attack
responsiveness.
the recipient’s body—is being
led by James Ferrara, MD,
“People with low-risk GVHD
DSc, Ward-Coleman Chair
are often overtreated,
James Ferrara, MD, DSc
in Cancer Medicine, and
exposing them to significant
Director of the Hematologic
side effects, while those
Malignancies Translational Research Center.
with high-risk GVHD are often undertreated,
allowing the disease to progress,” says
At its core is a new diagnostic test that was
Dr. Ferrara. “Our new scoring system
developed by Dr. Ferrara and a multicenter
provides for a personalized approach to
team of researchers, which predicts a
transplantation so that each patient gets the
patient’s response to GVHD treatment.
right treatment at the right time.”
Equally important, the scoring system is
paving the way for a new generation of
clinical trials that will test investigative
agents for the prevention and treatment of
acute GVHD. Dr. Ferrara’s ultimate goal is
to reduce mortality from the disease by 50
percent over the next ten years.
Recently, Dr. Ferrara created a consortium
of ten major stem-cell transplant centers in
the United States and Europe—the Mount
Sinai Acute GVHD International Consortium
(MAGIC)—to advance the science, which,
until now, has changed little in more than
40 years. The consortium expects to launch
a clinical trial later this year, making it the
first to treat GVHD using the biomarker
grading system.
Icahn School of Medicine at Mount Sinai | One Gustave L. Levy Place, Box 1128 | New York, NY 10029-6574 | www.icahn.mssm.edu/tisch
THE TISCH CANCER INSTITUTE
DIRECTOR’S REPORT | WINTER 2015
Enlisting the Body’s Immune System in the War Against Lymphoma
An innovative new vaccine that mobilizes
the body’s immune system to shrink tumors
in patients with low-grade B-cell lymphoma
has met with encouraging results in a clinical
trial at The Tisch Cancer Institute at the
Mount Sinai Health System. Of the study’s
first five patients, one experienced a complete
remission, another had a partial remission,
and the remaining three had stable disease.
of the Lymphoma Immunotherapy Program
at Icahn School of Medicine at Mount Sinai,
and the first researcher to use the new
dendritic cell mobilizing medicine as a
treatment for lymphoma. “Our patients find
this especially exciting because, in a sense,
they’re creating their own anticancer therapy,
as opposed to just passively receiving therapy,
as with standard treatments.”
The vaccine is produced in each patient
when two immune-modifying medicines
are administered directly into a tumor,
Joshua Brody, MD
combined with two days of localized, low-dose
radiotherapy. The first medicine mobilizes
special immune cells (dendritic cells) to the tumor site, where they
sample pieces of dying tumor cells after radiotherapy. The second
medication activates the tumor-loaded dendritic cells, which then
teach the effector arm of the immune system (T-cells) to recognize
and eliminate tumor cells throughout the body.
Traditional treatments such as chemotherapy and radiation enable
patients to live with low-grade B-cell lymphoma, but do not cure
the disease.
“We’ve helped a lot of people, but immune-based therapy has the
potential for even better outcomes,” says Joshua Brody, MD, Director
Sergei German, a patient enrolled in the trial,
notes that the treatment is an “opportunity
to treat lymphoma using immunotherapy
without resorting to harsh chemotherapy. It’s
like teaching our bodies to fight cancer the
same way they fight mumps.” The side effects, Mr. German reports,
have been very mild, similar to those of a flu vaccine for which he’d
typically take a pain reliever, like acetaminophen.
The Tisch Cancer Institute trial—soon to number 30 patients—is
being funded by a $750,000 Clinical Investigator Award from the
Damon Runyon Cancer Research Foundation. Dr. Brody recently
presented the study’s preliminary data at annual meetings of
the American Society of Hematology (ASH) Lymphoma Biology,
the American Association for Cancer Research (AACR) Tumor
Immunology, and the Society for Immunotherapy of Cancer (SITC).
Examining the Recurrence of Triple Negative Breast Cancer
Triple negative breast cancer
is an outlier in the world of
breast cancers, as it lacks
the three receptors (estrogen,
progesterone, and HER2),
and in many cases does not
respond to treatment.
within five years,” says
Dr. Shapiro. “I want to
gain a more thorough
understanding of the
differences between these
breast cancers that are
sensitive and resistant to
chemotherapy.”
At the Mount Sinai Health
System, nationally renowned
In collaboration with
researcher Charles Shapiro,
researchers at the Icahn
MD, Professor of Medicine,
Institute for Genomics
Charles Shapiro, MD
and Co-Director of the Dubin
and Multiscale Biology,
Breast Center at The Tisch
Dr. Shapiro is currently
Cancer Institute, is advancing the study of
evaluating the gene mutations and pathways
triple negative breast cancer.
of the sensitive and resistant cancers.
“Around half of the women with early-stage
triple negative breast cancer are cured with
standard chemotherapy, while the other half
will develop metastatic disease and die
“This may lead to a better understanding
of the biology of triple negative breast
cancer and may potentially identify new
drug targets and novel therapies,” he says.
In addition to his translational research,
Dr. Shapiro serves as Director of Survivorship
at The Tisch Cancer Institute, where he is
drawing upon his extensive background in
cancer survivorship to build a comprehensive
program at Mount Sinai.
“I am very excited about developing the
Cancer Survivorship Program throughout
the Mount Sinai Health System,” says
Dr. Shapiro. “There were nearly 14.5 million
cancer survivors in the United States
in 2014, and that number is expected to
increase to 19 million by 2024. That is a
testimony to our success in early detection
by cancer screening, improved treatments,
and supportive care. Equally important
is addressing the consequences of cancer
treatment and empowering survivors to
chart their own paths to optimal health
and well-being.” © 2015 Icahn School of Medicine at Mount Sinai | Marketing & Communications