Spring 2012 - The University of Chicago Medicine Comprehensive

Pathways to
®
Spring 2012 | cancer.uchicago.edu
Systemic Prostate Cancer Viewed as Chronic,
Manageable Illness
Walter Stadler, MD
M
are considered to
be an acute problem, but this
may no longer be true for prostate cancer. Systemic prostate cancer—or
prostate cancer that has spread—is now
considered a chronic disease.
“We can successfully manage prostate
cancer for years and even decades,” said
Walter Stadler, MD, Fred C. Buffett
Professor of Medicine and Surgery and
director of the Genitourinary Program.
One reason why the prostate cancer
program at UChicago is a “program of
distinction” is the vast and innovative
resources available to treat the entire
spectrum of the disease. A second reason
is the program’s integrative approach,
which incorporates the expertise of
multiple medical specialists.
“As a patient ages and the cancer
changes, we can incorporate novel therapies and standardized approaches based
on input from medical oncologists, as
well as radiation oncologists, urologists,
and geriatricians,” said Dr. Stadler.
ost cancers
New Therapies
Many new treatments for prostate cancer
are available, and many more are being
tested. Currently, UChicago has 25 open
prostate cancer clinical trials.
One avenue of pursuit is the development of therapies that target the stroma—
the tissue in which metastatic cancer
grows. In metastatic prostate cancer, the
most common metastatic site and stroma
is the bone environment. By targeting
the stroma, the cancer may have a significantly reduced opportunity to grow or
metastasize further.
Another avenue showing great promise
is immunotherapy. One such treatment,
sipuleucel-T, was FDA approved in 2010.
Researchers are now trying to determine
if using the bone-seeking radionuclide
samarium prior to a vaccine administration could also be effective. “We are
seeing some evidence in the laboratory
that radiation helps the immune system
respond better to vaccines, and we are
now testing this in patients,” explained
Dr. Stadler.
indolent that they will never
cause a problem for a patient
within his lifetime,” said Dr.
Stadler. “The real question
for 2012 and beyond is ‘How
do we identify those cancers
that will cause problems?’”
Knowing the difference is
the crux of the controversy
in prostate-specific antigen
(PSA) screening. Dr. Stadler
called the decision about
whether or not to undergo
PSA screening a “complex
medical decision” that needs
X-ray image of a prostate cancer patient with multiple bone
to take into account the
metastases.
patient’s age, family history,
A third avenue of pursuit involves a
race, prostate changes, and other factors.
seminal discovery at UChicago. In 1939,
His advice? “Don’t go to your local
Charles B. Huggins, MD, used hormone
library and take a blood test. Go to your
therapy to treat a 75-year-old man with
physician and discuss your unique situaprostate cancer. The man lived for
tion,” said Dr. Stadler.
another 13 years. In 1966, Dr. Huggins
UChicago physician-scientists, includwas awarded the Nobel Prize for his
ing Scott Eggener, MD, are using national
discovery that some cancers are dependent upon hormones, such as the male
sex hormone androgen.
“We are now re-discovering that the
androgen receptor remains a critical therapeutic target in this disease,” explained
Dr. Stadler. “Drugs, including the newly
approved abiraterone and a few others
in development, are effective in treating patients—even those with resistant
Walter Stadler, MD
disease.”
and international forums to address the
Biggest Challenges
overdiagnosis and treatment of prostate
Prostate cancer is second in incidence
cancer, while imaging experts, including
only to skin cancer in American men.
Aytekin Oto, MD, are developing better
The National Cancer Institute estimates
methods, such as magnetic resonance
there will be 242,000 new prostate cancer
imaging, to more accurately identify the
diagnoses this year, with 28,000 deaths
prostate cancers that require treatment.
from the disease.
The National Cancer Institute has
Yet, with the number of prostate
a booklet, “What You Need To Know
cancer cases expected to rise to 382,000
About™ Prostate Cancer,” available at
annually by 2030, Dr. Stadler said incicancer.gov/cancertopics/wyntk/prostate.
dence is not the real problem.
Learn more about the urologic cancer
“Not all prostate cancers need to be
team at UChicago Medicine at uchospitals.
treated. In fact the vast majority are so
edu/specialties/cancer/urologic.
The real question for
2012 and beyond is
“How do we identify
those cancers that
will cause problems?”
From the Director
The staggering amount of information we’ve gained from the
Human Genome Project and subsequent research continues to
help us understand why cells behave as they do—especially why
they go awry.
Michelle M. Le Beau, PhD
Our latest approaches to treating cancer involve identifying
molecular targets responsible for
cancer growth and then blocking,
or inhibiting, these triggers. But
because cancer can adapt and find
many escape routes, we are now
trying different combinations of
treatments.
Many of the stories in this issue
illustrate the impact of genomics
on cancer research.
Investigators have found that
simultaneously inhibiting one
molecular pathway in the cancer
cell and another in the area
surrounding the tumor (stroma)
can reverse growth in head and
cancer.uchicago.edu
neck cancer. The stroma is also the
target of new therapies for prostate
cancer.
One group of our researchers
has found that fatty tissue plays a
role in the spread of ovarian cancer,
while another may have discovered
a biomarker that can predict breast
cancer’s spread to the brain.
In this issue, we also spotlight
our Genomics Core Facility,
which gives researchers access to
state-of-the-art gene sequencing
technology. We also tell the story of
a makeup artist who helps patients
look and feel like their healthy
selves as they go through cancer
treatment.
Regards,
Michelle M. Le Beau, PhD
Director, The University of Chicago
Comprehensive Cancer Center
Arthur and Marian Edelstein
Professor of Medicine
Pathways to Discovery
KISS1 Protein May Hold Clue to Breast Cancer Spread
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cause of death
from breast cancer is not the
primary tumor, but from subsequent
tumors, such as those that spread to the
brain. One in five women with metastatic
breast cancer will contract a brain lesion,
and median survival for those patients is
less than a year after diagnosis, according
to the American Cancer Society.
Yet physicians currently have few tests
to predict which breast tumors will eventually spread to the brain and which will
not. Because no two patients’ cancers are
alike, physicians recognize that they need
reliable biomarkers to help predict how the
disease will progress and guide treatment
decisions.
Maciej Lesniak, MD, professor of
surgery and neurology and director
of neurological oncology, often treats
patients whose breast cancer has spread
to the brain. “Are there any risk factors or
biological phenomena behind this form of
the disease?” Dr. Lesniak asked. “That was
the question that we set out to answer.”
Treating cancer involves a collaborative
effort, as does finding predictive cancer
biomarkers. The ongoing search for factors
that can help physicians calculate the risk
of brain metastasis in breast cancer patients
has united researchers from multiple disciplines—neurosurgery, oncology, pathology,
and health studies—and multiple institutions—UChicago, University of Alabama at Maciej Lesniak, MD, is one of the nation’s leading neurosurgeons, specializing in neuro-oncology. He often treats patients whose breast cancer has spread to the brain.
Birmingham, and Kansas Medical Center.
of KISS1 expression exhibited slower disease progression
The first product of this large collaboration was the
and a reduced chance of developing brain metastases.
discovery of a promising biomarker with an innocuous
“KISS1 is an interesting protein that seems to at
name—KISS1—which was previously associated with the
least play a role in determining which subset of patients
progression of bladder, ovarian, and other cancers. The
develop brain metastases from breast cancer,” said Dr.
finding was published late last year in the journal Cancer.
Lesniak, senior author of the Cancer study.
KISS1 Associated with Reduced Metastatic Risk
More Research Necessary
Using tissue samples from the UCCCC’s Specialized
However promising the data, the researchers cautioned
Program of Research Excellence (SPORE) in Breast
that their study is only the first step toward establishing
Cancer, the research team, led by Ilya Ulasov, DVM,
KISS1 as a valid biomarker for predicting the course of
PhD, a research associate at UChicago, measured KISS1
Maciej Lesniak, MD
metastatic breast cancer. But if a mechanism is discovlevels in cancerous breast tissue, non-cancerous breast
ered, Dr. Lesniak speculated that KISS1 may hold clues
tissue, and brain lesions from metastatic cancer patients.
for slowing or preventing brain metastases.
and see whether it makes the tumor less aggressive
The comparison found lower levels of KISS1
“The question is ‘How can you modulate KISS1
or less prone to metastatic disease. It’s an interestprotein in the brain metastases relative to breast tumors,
expression for the benefit of patients?’” Dr. Lesniak
ing thought, but it’s probably too premature to know
suggesting that a reduction of this protein may be
asked. “One approach would be to restore KISS1 expres- whether that would hold true.”
associated with increased spread of cancer to the brain.
sion in patients with advanced metastatic breast cancer
Another analysis found that patients with higher levels
he most common
KISS1 is an interesting
protein that seems to at least
play a role in determining
which subset of patients
develop brain metastases
from breast cancer.
Open Cancer Clinical Trials
Patient enrollment is under way for more than 350 clinical trials at The University of Chicago
Comprehensive Cancer Center. Our new clinical trials include:
hase II trial of hippocampal avoidance during whole brain radiotherapy for brain metastases – Steven
P
Chmura, MD, PhD, principal investigator.
n P
hase I study of IPI926 plus FOLFIRINOX 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin in patients
with previously untreated, advanced pancreatic adenocarcinoma – Hedy Kindler, MD, principal
investigator.
n A
randomized Phase I trial of nanoparticle albumin bound paclitaxel (nab-paclitaxel, Abraxane®) with or
without mifepristone for advanced breast cancer – Gini Fleming, MD, principal investigator.
To learn more about these or any other UCCCC clinical trial, call toll-free 1-855-702-8222 for adult clinical
trials or 1-773-702-6808 for pediatric clinical trials, or go to cancer.uchicago.edu and click on Search Clinical
Trials in the blue box.
n
Pathways to
Executive and
Managing Editor
®
Pathways to Discovery is a quarterly publication of
The University of Chicago Comprehensive Cancer Center.
Spring 2012, Volume 7, Number 2
The University of Chicago Comprehensive Cancer Center
5841 S. Maryland Ave., MC1140, H212
Chicago, IL 60637
Phone: 1-773-702-6180
• Fax: 1-773-702-9311
[email protected]
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Writers
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Copy Reviewers
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Michelle M. Le Beau, PhD
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© 2012 by The University of Chicago Comprehensive Cancer Center.
All rights reserved.
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At the Forefront of Discovery®
Fat Cells Fuel Ovarian Cancer Growth
Ovarian cancer is dubbed the
“silent killer” because it often
goes undetected until it has spread
extensively; therefore, the ability
to control or prevent metastasis
would provide a significant advantage in treating ovarian cancer.
Researchers at UChicago are
moving in that direction because
they have determined why tumor
cells migrate to the omentum—
tissue that stores fat and protects
abdominal organs—and how the
tumors use fat cells to fuel their
growth.
When Ernst Lengyel, MD,
PhD, professor of obstetrics and
gynecology, watched surgeries as
Ernst Lengyel, MD, PhD
a resident, he wondered why most
as “jet fuel” for cancer growth, as Dr.
ovarian cancer spread to the omentum.
Little was known about the process except Lengyel described.
“The cancer cells go where the food
that once the cancer metastasized to the
is,” he said. “It’s a very natural selection,
omentum, it grew fast. This rapid growth
since fat is the highest and most energycontributes to the high mortality rate that
containing substrate we have in the body.”
results from ovarian cancer.
The study, which was published
With these clinical observations, Dr.
in Nature Medicine, illustrates how the
Lengyel set out to investigate the intertumor’s microenvironment may play a
action between ovarian cancer and the
bigger role in metastasis than previously
omentum. What he and his research team
suspected.
saw was that the cancer cells seemed to
be attracted to adipocytes, cells that store
fat. They injected ovarian cancer cells into Potential for New Treatments
Next, the researchers repeated the experithe abdomens of healthy mice and saw
that the cancer cells reached the omentum ment on genetically modified mice that
lacked a protein expressed by fat cells
within 20 minutes. They found that the
cancer cells used fat cells for energy, acting that is responsible for shuttling fat, called
Kristin Nieman, PhD
The cancer cells go
where the food is.
Ernst Lengyel, MD, PhD
fatty acid binding protein 4 (FABP4). The
researchers found that the cancer cells
did not grow as well on the omentum,
suggesting that FABP4 may be a target for
treatment.
“If you can stop the cells from growing there, you can prevent a major site of
metastasis,” said Kristin Nieman, PhD,
a postdoctoral fellow and lead author of
the study. “Hopefully, this will change the
Lab Findings Lead to Clinical Trial
for Head and Neck Cancer
A
paradigm for ovarian cancer, which has
not had many new treatments.” Current
treatment for ovarian cancer is tumor
debulking surgery and chemotherapy.
Further studies will determine how
these findings can benefit patients, as well
as how cancer cells adjust their metabolism when they interact with fat cells.
Dr. Lengyel said, “It should be helpful
to study and understand this mechanism
in other tissues that have adipocytes, such
as breast and brain tissue.”
A Little More With…
H. Rosie Xing, PhD
Assistant Professor of Pathology
If you were not a scientist, what would your
profession be?
A writer. I debated whether to study literature or
science and chose the latter, to be more “sane”
and emotionally conserved. I studied physics
before changing to biological science.
UChicago researcher is investigating
a question that has long puzzled cancer
specialists: Why does head and neck
cancer (HNC) have such a low response rate to a
commonly used treatment?
H. Rosie Xing, PhD, assistant professor of
pathology, has found a molecular connection that
may lead to more effective treatments for HNC,
which is the sixth most common cancer worldwide. Once the disease metastasizes, treatment
options are limited and patient survival drops to an
average of 10 months.
What’s playing in your office?
Jazz and Chinese Gu-qin (an ancient string
instrument)
If you could visit any research lab in the world,
where would it be … and why?
NASA’s research lab. I am always inspired by
updated knowledge about the birth and evolution of the universe.
The Study
The epidermal growth factor receptor (EGFR)
exists on cell surfaces and plays a role in regulatThe cancer cell-killing effect of this
ing cell growth. Dr. Xing said she became curious
combination is very evident.
when she learned that EGFR is overexpressed in
90% of HNC patients.
H. Rosie Xing, PhD
Dr. Xing collaborated with a computational
biologist and his research team to look at genomic informa- induce angiogenesis, the formation of new blood vessels to
fuel cell growth.
tion from clinical samples. Unlike other cancers, such as
Using a treatment that combined an EGFR inhibitor
breast and lung cancer, little has been studied about HNC
with an mTor inhibitor, the researchers saw that the EGFR
on a genomic level. In addition to EGFR, the researchers
inhibitor was effective at killing cancer cells, while the
studied mTor, a protein that also regulates cell growth.
mTor inhibitor was effective at depleting myofibroblasts
Dr. Xing discovered that when the mTor pathway is
and inhibiting angiogenesis.
blocked, cancer cells adapt by using EGFR, but when both
the mTor and EGFR pathways are simultaneously blocked,
The Next Steps
the tumor regresses. “The cancer cell-killing effect of this
Dr. Xing shared her research findings with Walter Stadler,
combination is very evident,” she said.
MD, Fred C. Buffett Professor of Medicine and Surgery,
Dr. Xing and colleagues also looked at changes that
and Tanguy Seiwert, MD, assistant professor of medicine,
occur when the tumor cells interact with the surrounding
who helped launch a randomized, Phase II multicenter
environment, known as the tumor stroma.
clinical trial to test this therapeutic combination.
Mark Lingen, DDS, PhD, associate professor of pathol “I think this is a prime example of translation where a
ogy and scientific director of the Human Tissue Resource
bench result may have direct impact on the clinical side,”
Center, compared cells from precancerous patients with
said Dr. Seiwert. “We really need a better treatment and this
cells from patients with HNC to determine differences in
seems like an avenue to try to develop one.”
the stroma.
UChicago is leading the trial, which is open at multiple
“We found there’s one component that is uniquely presacademic centers across the nation through the UCCCC’s
ent in the cancer state that is absent in the premalignant
Phase II Clinical Trials Network and the Mayo Clinic
state––myofibroblasts,” said Dr. Xing. Myofibroblasts
Cancer Research Consortium. Dr. Seiwert said he expects
produce collagen and can change the structure of a tumor.
to have results in approximately 1 year.
Previous studies have shown that aggressive breast and
pancreatic cancers are rich in myofibroblasts, which may
cancer.uchicago.edu
What projects are you working on at home?
I am assembling pictures of my kids from their
birth until now to make photo albums. I am also
writing down how much they have enriched
my life.
Who is the person you most admire?
The Greek philosophers: Thales, Pythagoras, Heraclitus, Parmenides, and Democritus. They showed
us our capability to wrap our thoughts to explain
the diversity of nature. The Athenian philosophers
Socrates, Plato, and Antisthenes showed us how
knowledge can be elevated to ideas.
What was the last book you read?
A Chinese novel, The Flowers of the War, by
Chinese-American writer Yan Gelin for my book
club. It is about the Nanjing Massacre, which
happened in my hometown, Nanjing, during the
Japanese invasion.
What is the most daring thing you have ever
done?
Coming to study in North America (Canada) at
the age of 19. Twenty-three years later, I truly feel I
am both Chinese (my roots) and North American
(my intellectual re-birth).
If you had one piece of advice for someone
considering your field, what would it be?
Make sure you feel that being a scientist is a way
of life, not a way of living. Once you are in, keep a
humble heart, a curious mind, and the respect for
life to uncover the cause of diseases.
3
Pathways to Discovery
Makeup Restores Cancer Patients’ Image, Improves
Quality of Life
O
ncology patients at UChicago have access
to a free service that gives them a greater
sense of control over their cancer. They can
schedule a private session with Lori Ovitz,
who drew from a 20-year career as a makeup artist for
celebrities and models to create tips and techniques to
help cancer patients look and feel like their healthy selves.
While researchers at The University of Chicago are
developing new ways to effectively prevent, diagnose, and
treat cancer, many of today’s cancer treatments carry side
effects. This may make confronting
the mirror a difficult experience
for patients who may see tired
circles around their eyes; thinning
or nonexistent hair, eyebrows, and
eyelashes; a blotchy complexion;
and a gaunt or puffy face.
Of these side effects, hair loss
can be the most challenging. “A lot
of people are more worried about
losing their hair than they are their disease,” Ovitz said.
She said many patients are concerned about being stared
at by strangers, scaring their young children, and worrying their families.
Looking Like Yourself
Ovitz shows cancer patients techniques for evening out
skin tone, returning color to the face, covering scars,
and—perhaps most importantly—using makeup to create
natural-looking eyebrows and eyelashes.
“It’s not about using makeup to look like a beauty
queen,” Ovitz said. “It’s about using makeup to look like
yourself—a healthy version of yourself.”
She said when patients view themselves in a mirror
after their makeover, they instantly feel uplifted, energetic, and more confident. Ovitz recalled one woman
who, for many months avoided leaving her house,
BEFORE
Lori Ovitz shows cancer
patients techniques for
evening out skin tone,
covering scars, and using
makeup to create naturallooking eyebrows and
eyelashes. Her book,
Facing the Mirror with
Cancer, is a step-bystep guide to applying
makeup and includes
chapters about skincare
and wigs written especially for cancer patients.
AFTER
suddenly felt like going dancing
with her husband after she
received a makeover.
“If I can provide care for
someone on the outside, they
automatically feel rejuvenated
on the inside. It gives people a
more positive outlook as they go
through treatment,” said Ovitz.
Patients at UChicago can learn
Lori Ovitz
about Ovitz’s services through the
Cancer Resource Center, which
is a partnership between the UCCCC and the American
Cancer Society that connects oncology patients with
information about cancer, support groups, financial
assistance, and other aspects of cancer care.
Ovitz provides doctors and patients at UChicago
with free copies of her book, Facing the Mirror with Cancer,
which is a step-by-step guide to applying makeup and
includes chapters about skincare and wigs written
especially for cancer patients.
Ovitz and her husband, Bruce,
a 40-year cancer survivor, selfpublished the book and donated
a large portion of the proceeds to
cancer research. Ovitz serves as a
member of the Board of Trustees
of The University of Chicago
Cancer Research Foundation, and
she is a board member of Comer
Children’s Hospital.
Ovitz also travels around the
country to participate in workshops at top cancer centers,
but her home base for the past 12 years has been at
UChicago. She visits with children and teens at Comer
Children’s Hospital each week, bringing them toys and
helping them feel better enough about themselves to
return to school.
Ovitz said, “Makeup can’t cure cancer, but it can help
patients face the mirror.”
If I can provide care
for someone on the
outside, they automatically feel rejuvenated
on the inside.
We Give Thanks to Our Littlest Donor
Comer 2 Opens
T
second floor of
Comer Children’s Hospital is now open. Comer 2 is
designed to increase care and comfort for patients and their
families. The new floor houses the pediatric infusion area, pediatric
sedation service, and the newly created Center for Childhood Cancer
and Blood Diseases.
Chicago artist Greg Gove
created murals in the Center
for Children and Specialty
Care. One of his murals
is an enormous tree filled
with birds and bird houses.
“We want it to feel fun. The
whole floor looks like spring
or summer,” said Gove.
he new
(front, from left) Brayton Alley and Pittman Alley. (back, from left) Ernst Lengyel, MD, PhD,
Michelle Le Beau, PhD, and Hilary Kenny, PhD
Six-year-old Pittman Alley from Lake Forest received a behind-thescenes tour of a cancer research lab at UChicago. Pittman donated
$50 to The University of Chicago Cancer Research Foundation (UCCRF)
to support ovarian cancer
research. His parents also
support the UCCRF.
Postdoctoral Fellow Hilary
A. Kenny, PhD, described
Pittman as “a very observant
and curious little gentleman.”
In fact, Pittman won a lab
competition by identifying
which test tube contained the
most protein.
Pittman gives UCCCC Director Michelle Le Beau,
PhD, a check for $50 to support cancer research at
UChicago.
4
cancer.uchicago.edu
At the Forefront of Discovery®
Member News & updates
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1 Bana Jabri, MD, PhD, was named vice chair for basic
research for the Department of Medicine (DOM). Dr. Jabri,
an expert in celiac disease, joined other newly appointed
vice chairs Julian Solway, MD, and Ravi Salgia, MD,
PhD, as members of the restructured DOM Research
Advisory Committee. They will work together to develop
new programs and initiatives that will advance research
at UChicago.
2 Associate Professor of Medicine Lucy Godley, MD,
PhD, was elected to the American Society of Clinical Investigation, one of the nation’s oldest and most respected medical honor societies. Dr. Godley was chosen for
her important contributions to cancer biology research,
specifically her work in uncovering the molecular mechanisms that drive tumorigenesis.
3 Susan Lerner Cohn, MD, professor of pediatrics, has
been elected to serve a 3-year term as treasurer of the
American Society of Clinical Oncology (ASCO). Dr. Cohn
is the director of pediatric clinical sciences at Comer
Children’s Hospital and focuses her research on neuroblastoma. She will begin her term as ASCO treasurer in
June 2012.
4 Olatoyosi Odenike, MD, was promoted to associate professor of medicine. As a clinician, Dr. Odenike
provides expert care to adult patients with leukemia,
chronic myeloproliferative diseases, and myelodysplastic
syndromes. Her research centers on developing novel
therapeutic agents for the treatment of these diseases.
5 Mitchell C. Posner, MD, Thomas D. Jones Professor
of Surgery and chief of the Section of General Surgery
and Surgical Oncology, has assumed the role of medical
director of clinical cancer programs at The University of
Chicago. Dr. Posner, an internationally recognized expert
in gastrointestinal cancers, will lead UChicago’s efforts to
develop a strategic plan for cancer services. He will also
help build an implementation plan to increase clinical
volume and raise the cancer program’s profile.
6 Janet Rowley, MD, DSc, Blum-Riese Distinguished
Service Professor of Medicine, was presented with the
prestigious Ernest Beutler Prize at the American Society
of Hematology Annual Meeting in San Diego. She was
also awarded the 2012 Japan Prize for Healthcare and
Medical Technology for her part in the development of
the first precisely targeted anti-cancer drug, imatinib
(Gleevec®).
Three UCCCC members have been honored with named
professorships. A named professorship is the highest
academic honor accorded by a university and is awarded
only to the most distinguished scientists and clinicians.
7 Habibul Ahsan, MBBS, MMedSc, is the Louis Block
Professor of Health Studies, Human Genetics, and Medicine. He is also director of the Center for Cancer Epidemiology and Prevention and UCCCC associate director for
population research. 8 David H. Song, MD, MBA, is the
Cynthia Chow Professor of Surgery. He is also vice chair of
the Department of Surgery, chief of the Section of Plastic
and Reconstructive Surgery and director of the Residency
Training Program. 9 Jerrold Turner, MD, PhD, is the Sara
and Harold Lincoln Thompson Professor of Pathology.
10 Yingming Zhao, PhD, has been promoted to professor in the Ben May Department for Cancer Research.
Dr. Zhao focuses his research on cellular interactions,
proteomics, systems biology, and protein post-translational modifications.
cancer.uchicago.edu
Newly Hired Faculty
11 Yusuke Nakamura, MD, PhD, secretary general of
the Japanese Government’s Office of Medical Innovation
and a professor of molecular medicine at Tokyo University’s Human Genome Center, will join the UChicago
faculty in April. As professor of medicine, Dr. Nakamura
plans to apply his expertise in cancer research and pharmacogenomics to his work on personalized medicine.
12 Andrzej Jakubowiak, MD, PhD, joined UChicago as
a professor of medicine in the Section of Hematology/
Oncology and as director of the Myeloma Program. Dr.
Jakubowiak is a national leader in the development of
new drugs for the treatment of multiple myeloma.
13 Alexander Langerman, MD, is an assistant professor of surgery whose principal research focuses on the
diagnosis and treatment of cancers and other tumors of
the head and neck. He also has experience and interest
in emerging trends in patient-physician communication
and surgical education.
New Melanoma Book Focuses Entirely
on Therapeutics
The first book on melanoma devoted
entirely to targeted therapeutics has
been published and was edited by
Thomas Gajewski, MD, PhD, professor of pathology. The book describes
both established signal transduction
inhibitors, as well as emerging
molecularly guided immunotherapies
and includes the most up-to-date
data from current clinical Phase I-III trials.
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Pathways to Discovery
Research Highlights
The following represent some of the research accomplishments
of UCCCC members published November 2011–February 2012.
New Image-Guided Radiation Therapy
May Help Some Lung Cancer Patients
A new form of radiation treatment may
control tumor growth and prevent further
metastasis in patients with non-small cell
lung cancer (NSCLC) that has not spread
widely.
A recently published study showed that
hypofractionated image-guided radiation
therapy (HIGRT) can control individual
tumors and may improve long-term
progression-free survival in patients
with NSCLC that has spread to five sites
or fewer, a stage called oligometastasis.
HIGRT consists of several large doses of
radiation administered several times over
a 2-to-3 week timeframe. In this study,
25 patients who had previously received
HIGRT were evaluated.
Investigators included Daniel Haraf,
MD, MS, professor of radiation and
cellular oncology, Ralph Weichselbaum,
MD, D.K. Ludwig Professor of Radiation &
Cellular Oncology, Ravi Salgia, MD, PhD,
professor of medicine, Victoria Villaflor,
MD, assistant professor of medicine, Philip
Hoffman, MD, professor of medicine,
Steven Chmura, MD, PhD, assistant
professor of radiation and cellular oncology, Philip Connell, MD, associate professor of radiation and cellular oncology,
and Everett Vokes, MD, John E. Ultmann
Professor of Medicine.
(Hasselle et al., J Thorac Oncol 7:376-381, 2012)
Study Explains Low Colorectal Cancer
Screening Rate in Chinese American
Immigrants
Screening for colorectal cancer, the second
leading cause of cancer death in the U.S.,
is not widely practiced among the Asian
American population. To learn why, Karen
E. Kim, MD, MS, associate professor of
medicine, and her research team analyzed
cancer screening behavior in a group of 113
Chinese American immigrants.
The researchers found that participants
with primary care physicians were more
likely to have undergone colorectal cancer
screening in the past, and that the longer
the participants lived in the U.S., the
more likely they were to have a primary
care physician. Furthermore, nearly half
of all Chinese men and Chinese women
perceived no risk for colorectal cancer.
After attending a culturally tailored
educational session on colorectal cancer
screening, which included bilingual
staff, more than 70% of the participants
Just the
Stats
(Kim et al., J Immigr Minor Health published online
ahead of print, December 2011)
Diabetes Drug Boosts Survival in
Patients with Ovarian Cancer
Metformin, a drug used to lower glucose
levels may improve survival in ovarian
cancer patients with type II diabetes.
A UChicago team retrospectively
studied more than 300 patients to learn
if a relationship exists between diabetes
medication and ovarian cancer treatment
outcomes. They found that patients with
type II diabetes who used metformin
had improved progression-free survival
compared with nondiabetic patients and
diabetic patients not using metformin,
despite receiving the same treatment for
ovarian cancer. These findings could lead
to treatments using a patient’s metabolism
to modulate treatment response. The
authors are now planning prospective studies to verify these findings.
Members of the research team included
lead author Iris Romero, MD, assistant
professor of obstetrics and gynecology,
Theodore Karrison, PhD, associate
professor of health studies, S. Diane
Yamada, MD, professor of obstetrics
and gynecology, and senior author Ernst
Lengyel, MD, PhD, professor of obstetrics
and gynecology.
(Romero et al., Obstet Gynecol 119:61-67, 2012)
Gene Signature Predicts Poor Survival
Outcome in a Subtype of Glioblastoma
Researchers have developed a method to
predict the survival outcome for patients
with glioblastoma multiforme (GBM), an
aggressive brain cancer with typically poor
prognosis.
The team, including Ralph Weichselbaum, MD, D.K. Ludwig Professor of
Radiation & Cellular Oncology, isolated
eight genes related to the Interferon/STAT1
pathway and found that overexpression
of these genes predicted poor survival
outcome in patients with GBM. Genes in
this signaling pathway have previously
been associated with resistance to radiation therapy in head and neck and breast
cancer.
Amittha Wickrema, PhD, associate professor of medicine and director of the Clinical Stem Cell Laboratory,
prepares blood stem cells for culturing in a sterile environment.
Additionally, the researchers demonstrated that the gene signature was dependent on the cancer subtype and said this
study has implications for understanding
the molecular mechanisms responsible for
tumor progression and response to therapy.
associated with overall survival in patients
newly diagnosed with Stage IV NSCLC.
Larger clinical studies will be required
to validate the use of whole-body tumor
burden for prognostic purposes.
(Duarte et al., PLoS ONE 7:e29653, 2012)
MicroRNA Behavior May Contribute
to Colorectal Cancer in Patients with
Chronic Ulcerative Colitis
New research sheds light on the process
by which colon cancer develops in patients
with inflammatory bowel disease.
A research team led by Marc
Bissonnette, MD, associate professor
of medicine, found decreased expression of microRNA-143 (miR-143) and
microRNA-145 (miR-145) in colonic cells
of patients with chronic ulcerative colitis.
They speculate that this downregulation
may predispose patients to developing
colorectal cancer.
MiR-143 and miR-145 form a gene
cluster that was previously reported to
suppress colon tumors. Further studies
of these microRNAs will help researchers
gain insight into cancer development in
patients with inflammatory bowel disease.
Alessandro Fichera, MD, associate
professor of surgery, and David Rubin,
MD, associate professor of medicine, were
also involved with the study.
Protein Kinase Found to Extend
Dormancy of Metastatic Prostate
Cancer
UChicago scientists are one step closer
to understanding the molecular factors
that control the growth of disseminated
prostate cancer cells.
Prostate cancer cells often travel to
distant sites during the early stages of
tumor development and remain undetected
for extended periods of time, eventually
leading to recurrence after the primary
tumor has been treated. New research by
Russell Szmulewitz, MD, assistant professor of medicine, Carrie Rinker-Schaeffer,
PhD, professor of surgery, Kay Macleod,
PhD, associate professor in the Ben May
Department for Cancer Research, and
colleagues, indicates that protein kinase
MKK4 suppresses the growth of metastatic
prostate cancer cells. This research will
facilitate the development of new therapies
aimed at keeping malignant cells dormant.
(Szmulewitz et al., Int J Cancer 130:509-520, 2012)
Imaging Aids in Prognosis of Patients
with Late-Stage Lung Cancer
Researchers have found that PET/CT imaging can help predict the treatment outcome
of patients with Stage IV non-small cell
lung cancer (NSCLC).
In a retrospective study, Kenji Suzuki,
PhD, assistant professor of radiology, and
colleagues evaluated baseline whole-body
tumor burden using PET/CT imaging.
Baseline measurements were significantly
Donations to The University of Chicago Cancer Research Foundation (UCCRF) provide the seed money
for promising cancer research projects. As these projects mature and are recognized by the federal
government, grant funding increases exponentially. Examples of return on investment (ROI) include:
Personalized Therapies
for Prostate Cancer
Immunology Research for
Acute Myeloid Leukemia
Donald Vander Griend, PhD
Justin Kline, MD
2010
$50,000 UCCRF
2010
$25,000 UCCRF
2011
$215,000 government
funding
2011
$175,000 government
funding
ROI: 330%
6
completed a free fecal occult blood testing
screening.
The authors wrote that future research
and interventions that address knowledge
deficits and focus on culturally tailored
healthcare access may have the potential to
increase colorectal cancer screening among
Chinese American immigrants.
Breast Cancer Research
Geoffrey Greene, PhD
2001
ROI: 600%
$15,000 UCCRF
2002- $10,000,000 government
2011 funding
ROI: 66,600%
cancer.uchicago.edu
(Liao et al., Acad Radiol 19:69-77, 2012)
(Pekow et al., Inflamm Bowel Dis 18:94-100, 2012)
Scientists Confirm Tumor Suppressor
Gene in Cervical Cancer
Researchers at UChicago have demonstrated that NOL7 functions as a tumor
suppressor gene in cervical cancer.
Mark Lingen, DDS, PhD, associate
professor of pathology, and colleagues
found that NOL7 expression is significantly
decreased in cervical cancer cells, and
that the gene harbors tumor-associated
mutations that may potentially inactivate
its tumor suppressor function. Dr. Lingen’s
lab reported the discovery of NOL7 in a
paper published in Oncogene in 2005. These
findings, together with a previous study
demonstrating that the reintroduction of
NOL7 in cervical cancer cells suppresses
tumor growth by 95%, support NOL7 as a
tumor suppressor.
For the study, Dr. Lingen collaborated
with Ravi Salgia, MD, PhD, professor of
medicine, Lucy Godley, MD, PhD, associate professor of medicine, and Kenan Onel,
MD, PhD, associate professor of pediatrics.
(Doçi et al., Int J Gynecol Pathol 31:15-24, 2012)
At the Forefront of Discovery®
UChicago Expertise Makes a Difference
for Melanoma Patients
A
aerobics instructor, Irene
Cornwell knows how to motivate
people to push their bodies to
new levels. Her upbeat attitude proved
invaluable during the most trying time in
her life—when she faced cancer.
In 2005, the fit mother of three saw
her family physician about a lump on her
neck. A surgical biopsy revealed it was
melanoma, the most serious type of skin
cancer.
Within 24 hours of her diagnosis,
Cornwell met with doctors at UChicago.
A positron emission tomography scan
revealed that the cancer was at Stage 3A,
meaning it had infiltrated the lymph
nodes. After surgery to remove the
nodes in her neck, Cornwell underwent
treatment with interferon, an immune
therapy.
host’s immune system. Armed with that
information, researchers are able to offer
effective new therapies.
s an
A Positive Outcome
The side effects were brutal. Flu-like
symptoms and fatigue kept Cornwell in
bed for 12-13 hours per day. What she
said helped her morale was teaching water
aerobics to senior citizens once a week.
She also credited the support of her
family, friends, and employer, as well as
her care team at UChicago. She recalled
how her nurse coached her over the
phone as she gave herself her first home
injection of interferon.
Now, 7 years later, Cornwell, who
Irene Cornwell, pictured with husband John, is one of
many melanoma survivors who has been treated at
UChicago, where newly developed therapies are helping patients live longer.
lives in southwest suburban Frankfort,
comes to UChicago for her yearly
appointment and has maintained the
status of “no evidence of disease.”
She is one of the lucky ones. Since
her cancer did not metastasize to other
organs, she had a good shot at beating it.
In patients whose disease has advanced
past the lymph nodes, however, surgery
is not an option—and more aggressive
therapies are needed.
The prognosis has typically not been
good for these patients, but that is rapidly
changing. Researchers have made great
advances in studying the tumor’s biology and understanding how it evades the
New Therapies for Melanoma
Two breakthrough therapies for metastatic melanoma were approved last
year— ipilimumab, an immune therapy,
and vemurafenib, which inhibits the
B-Raf enzyme involved cell growth.
Researchers at UChicago contributed to
the development of both of these drugs.
The results are encouraging.
About half of advanced cases have
the B-Raf mutation and can be treated
with vemurafenib. The majority of those
patients see their tumors shrink, according to research published in The New
England Journal of Medicine last year.
With ipilimumab, only 10%-15% of
patients experience tumor shrinkage but
about 40% of patients are alive at the
1-year mark, and 20% survive to at least 2
years.
“More than half of our patients have
some kind of clinical benefit now with
the new therapies, which is extraordinary
compared to where we were a few years
ago,” said Thomas Gajewski, MD, PhD,
professor of medicine, who treated Cornwell.
He added that there are additional new
drugs in development that may be even
more effective.
More than half of our
patients have some kind
of clinical benefit now
with the new therapies,
which is extraordinary
compared to where we
were a few years ago.
Thomas Gajewski, MD, PhD
“We have to keep figuring out the
reason why the tumor sneaks through
so we know which new drugs to add,”
he said. The new melanoma therapies
are a prominent example of personalized
therapy, in which the treatment is based
on the biology of the tumor, rather than a
one-size-fits-all model.
Despite new therapies, Dr. Gajewski
cautioned that melanoma incidence is
on the rise. People with light hair, light
skin, and light eyes are at increased risk
for sunburn and sun damage mutations.
Sunburn during childhood or teenage
years seems to increase a person’s risk for
melanoma.
Cornwell, who is a redhead, remembered tanning—or burning—on Oak
Street Beach as a teen. “Nobody knew in
those days,” she said. “Now we know, and
we can take care of the next generation.”
Focus on:
Core Facilities
Next-Generation Sequencing Delivers Faster
Genomic Information for Researchers
Since cancer is a complex biologic
process triggered by genetic changes,
knowing where to look among the threebillion-DNA base pairs in the human
genome would be nearly impossible without the aid of the latest DNA sequencing
machines and computer analysis tools.
“Modern technology has the ability to
sequence whole genomes in days,” said
Pieter Faber, PhD, operational director of
UChicago’s Genomics Core Facility.
Through the Genomics Core, researchers have access to sophisticated technology
that can monitor and explore the genome
at unbelievable speeds. In the past year, the
facility has acquired two LifeTech SOLiD™
5500xl systems to perform next-generation
sequencing and the Illumina HiScanSQ
system, which can perform next-generation
sequencing and microarrays, used to
measure gene expression.
The first human genome sequence
was determined by sequencing 10,000
base pairs at a time. Next-generation
technology allows for much higher
throughput and greater sensitivity. “The
newer machines can sequence a couple
of billions of base pairs in one run,” said
Dr. Faber. “Next-generation sequencing
is taking genomics to a whole new level.”
Dr. Faber explained that the original purpose of the technology was to
sequence whole genomes, but researchers soon realized high-throughput
sequencing can answer many of the same
questions as microarrays but provide
much more robust data.
The facility, which is located on
campus at the Knapp Center for
Biomedical Discovery, offers researchers
state-of-the-art genomics capabilities, as
well as data analysis services in partner-
Pieter Faber, PhD, operational director of the Genomics Core, shows off the new next-generation DNA sequencing
technologies available.
ship with a new bioinformatics core being
developed by Robert Grossman, PhD,
professor of medicine and chief research
informatics officer.
These new capabilities will help predict
cancer behavior and response to therapy,
which will ultimately help design personalized cancer therapies.
Next-generation
sequencing is taking
genomics to a whole
new level.
Pieter Faber, PhD
Caregivers Learn About a Healing Touch
The UCCCC Office of Community Engagement and
Cancer Disparities (OCECD) partnered with the
Chinese American Service League (CASL) to host a
unique presentation for home health professionals
who care for cancer patients.
Integrative health expert William Collinge, PhD,
MPH, explained how caregivers can use touch to
reduce a cancer patient’s symptoms of distress.
The presentation, “Touching, Caring, and Cancer,”
was based on his book and DVD by the same name.
About 30 people attended the event, held at
CASL in Chicago’s Chinatown neighborhood.
cancer.uchicago.edu
7
Pathways to Discovery
Valentine’s Karaoke Raises Money for Cancer Research
The University of Chicago Cancer Research Foundation (UCCRF) Associates Board hosted a Valentine’s event at Lottie’s Pub in Chicago to
raise money for cancer research. More than 100 people attended Karaoke for a Cure and contributed $4,500 to the UCCRF.
Shubitz Cancer Prize
Monday, May 21
Hotel Sofitel Chicago Water Tower
T
he 2012 Simon M. Shubitz Cancer Prize will be
bestowed upon Joe
Gray, PhD, a renowned genomics expert at Oregon Health
& Science University’s Knight
Cancer Institute, who is taking
a lead on making personalized
cancer medicine a reality for
all patients. The Shubitz Prize
recognizes excellence in cancer Joe Gray, PhD
research and brings to UChicago internationally
renowned scientists who have made significant
contributions to the field of cancer.
Event Chairs Sheila Mulligan and Kate Crouch
Rae Allen and Lauren Siegel
Southwest Suburban
Salons Host Stylish
Fundraiser
Stylists at two hair salons in Orland Park
gave up their usual Sunday day off from work to
participate in a Cut-a-Thon for cancer research.
The salons, Salon Salon and neighboring Salon
151, donated 100% of the proceeds from the event
to United-4 A Cure, which is run by four sponsors
including the nearby Riviera Country Club and
Sports Center.
Last year, United-4 A Cure donated $15,000
to UChicago cancer researcher Vani J. A. Konda,
MD, for her work on nanocompounds for the
(from left) Salon Salon stylists Denise Neubauer, Kelly Powell, Ken Malito, Tracy Labriola,
and Donna Sanders.
early detection of colon cancer.
Pathways to
Spring 2012
cancer.uchicago.edu
®
In this issue…
1
Prostate cancer is now considered a
chronic disease.
3
4
2
A biomarker may help identify
which breast cancers will spread to
the brain.
3
Researchers explain why ovarian
cancer cells spread to fatty tissue.
The University of Chicago Medicine
5841 S. Maryland Ave., MC1140 H212
Chicago, IL 60637
[email protected]
save the date
Jacquelyn McCanse and Rae Allen
A targeted drug combination may
improve treatment outcomes in
head and neck cancer.
A volunteer shows cancer patients
how makeup can improve their
quality of life.
7
As melanoma cases rise, UChicago
experts offer patients advanced
therapies.
Support cancer research
through the UCCRF:
cancer.uchicago.edu/donations