Download Breast Cancer-Killing The Last Cell

S a m u e l Wa x m a n C a n c e r R e s e a r c h Fo u n d at i o n
REP RT
Spring 2006
Breast Cancer-Killing The Last Cell
UNDERSTANDING STEM CELLS AND DIFFERENTIATION
TUMOR CELL
cells can produce a whole new tumor.
CANCER STEM CELL
“In many tissues a small number of stem cells give
rise to a larger number of proliferating cells and then
the proliferating cells generate cells that differentiate
and form the final tissue,” says Dr. Neel, who is also
1. Original tumor
2. After treatment
3. Tumor regrows
But, if treatment can be tailored to differentiate and kill
cancer stem cells, they may destroy the tumor permanently.
Professor of Medicine at Harvard Medical School. “To
give you an idea, in a mouse, total bone marrow has
about 20 million cells. Only about ten thousand of
those are stem cells. Yet one of those cells, if purified,
Illustration by Barbara Taff
could give rise to the entire bone marrow.
“Since the tumor stem cell has infinite self-renewal
capability, it can just grow back,” says Dr. Neel.“And it
1. Original tumor
Source: Science News
2. After treatment
3. Tumor shrinks,
no regrowth
can grow back with more mutations which make it
more difficult to kill.”
Dr. Neel and his colleagues are trying to demon-
A
t the age of thirty-six, a friend we’ll call
strate that what has been learned about tumor hier-
Sandra needed a lumpectomy and radia-
archy in research on leukemias also applies to breast
tion for breast cancer. Her recovery was
cancer. Both mouse and human models are helping
uneventful; she called her cancer “a thing of the past.”
him and his coworkers toward that goal, and to
That was twenty-three years ago. Recently, a recur-
develop ideas about how to target tumor stem cells
rence necessitated a mastectomy. This time Sandra’s
selectively, with drugs. “The ultimate goal is to use
recovery has been difficult, and now her doctors are
biopsy to identify tumor stem cells and determine
“discouraged.” Unfortunately, her story is familiar.
their self-renewal and survival characteristics,”Dr. Neel
(continued on page 7)
Researchers whose goal is to eradicate breast cancer
the first time around are looking for the reasons
Sandra and so many other women have breast cancer
recurrences after a long period of health.
Building on work done by John Dick with leukemias
in the late 1990s, Dr. Ben Neel, the Director of the
Cancer Biology Program at Beth Israel Deaconess
Inside
2
From the Chairman & Scientific Director
3
Research Highlights
4
Fundraising Events
6
News Briefs
Medical Center in Boston is investigating the idea that
a small population of cells is responsible for tumor formation. In the past, before the molecular age in cancer
biology, many scientists believed all tumor cells were
more or less the same. Now more researchers think
that the vast majority of cells help cancer grow and
spread but just a few chemotherapy-resistant stem
8 Special Events Calendar
Research Highlights
s a m u e l wa x m a n
cancer research
f o u n d at i o n
OFFICERS OF THE BOARD
CHAIRMAN
Michael Nierenberg
85% of all funds raised will go
directly into cancer research.
VICE-PRESIDENTS
Gary Jacob
J. Jay Mautner
Dena K. Weiner
Samuel Waxman, M.D.
Michael Nierenberg
From the Chairman & Scientific Director
Dear Friends,
Y
defeat breast cancer. Although more
women will get breast cancer, better education leading to earlier diagnosis and
2006 is off to an incredible start!
ication to our mission, Dr. Ethan Dmitro-
coordinated treatment by surgeons, med-
Our “Collaborating for a Cure” Benefit
vsky has joined Dr. Jonathan Licht as Asso-
ical and radiation oncologists and genetic
raised a record breaking $2.8 million.
ciate Scientific Director. Dr. Dmitrovsky is
advisors is leading to a higher cure rate and
Because of your generosity we continue
the Andrew G. Wallace professor at Dart-
a decrease in mortality. This achievement
to fund vital research programs all over
mouth Medical School, and the Chairman
has required billions of dollars, worldwide
the world so that one day our children
of the Department of Pharmacology and
innovative research, government commit-
can live in a world without cancer.
Toxicology. He also serves as a member of
ment and women’s advocacy pressure.
As you will read in News Briefs and
Milestones, we’ve made significant
tific Advisory Board.
How then does a small foundation such
as SWCRF contribute to this massive com-
progress in treating leukemia and other
By this time next year, our
forms of blood malignancies. We also
researchers will be able to log on to a
As you will read in this newsletter, the
report on two breakthroughs in science:
secure site and share their latest findings.
SWCRF is focusing on the tragedy of late
new and specific treatments of mel-
What makes our Foundation unique is its
recurrence of breast cancer due to dormant
anoma and lung cancer and basic research
insistence that our researchers collabo-
and cancer stem cells. Dormant cancer cells
in breast cancer stem cells which will
rate. As grants are awarded only upon
are difficult to detect, treat and can revert to
result in saving more lives in the not-so-
proof of this collaboration, this site will
aggressive growing tumor-forming cells.
distant future.
bring us to a new level of
SWCRF scientists have found a specific
This year, we will continue to expand
our research in the fields of Breast, Lung,
Prostate, Liver and Pancreatic Cancer,
Leukemia and Lymphoma, Melanoma,
Aberrant Gene Expression and Preventing
Metastasis. We are just now receiving
applications for our 2006 granting cycle.
Not only has this impressive pool grown
in size but it also contains applicants from
top research institutions, one of which
includes a Nobel Laureate. Most importantly, 85% of all funds raised will go
directly into cancer research.
To sustain this level of activity and ded-
2
the Lance Armstrong Foundation Scien-
greatly
enhanced communication.
To add to this year’s excitement, we
have just hired a new Director of Development, Mark Silverstein. He joins us with
15 years of solid fundraising experience,
most recently with The Skin Cancer Foundation and the American Red Cross. We
look forward to announcing his great
achievements in future newsletters.
All this, of course, could never be
possible without your support, energy
and commitment. For this we are enormously grateful.
– Michael Nierenberg
SECRETARY
Laurie L. Schaffran
TREASURER
Gary Gladstein
es, we are winning in the battle to
mitment to beat breast cancer?
signal to block this reversion, and inhibitors
have been developed which may become
drugs that can be used to kill the dormant
cancer cells.
A close cousin to the dormant cancer cell
may be the breast cancer stem cell, the
mother lode that gives birth to each tumor.
The SWCRF is funding outstanding work to
solve the riddle of the breast cancer stem
cell and expose its Achilles heel, so that a
specific treatment can be developed.
The SWCRF breast cancer program is
expanding. It includes research projects to
identify nonfunctioning genes that cause
(continued on page 7)
Max Wicha, Committed
Cancer Sleuth
BOARD OF DIRECTORS
Lawrence Altman
Philip T. Brudner
Peter Claman
Robert E. Fischer
Arminio Fraga
Judi Gladstein
Eric Goldstein
Clifford Greenberg
Linda Herman
Mary Kantor
Costas Kondylis
Leslie Elliot Krause
Abner Levine
Mildred Levine
Shumer S. Lonoff*
Thomas Marano
Richard Mazer
Alfred J. Seaman†
Edward Sheldon
Howard Shlafmitz
Tony M. Shogren
Clifford Sterling
Spencer Waxman
David T. Workman*†
HONORARY BOARD
Maureen Cogan
Martin L. Coyne
Susan W. Rose
Selma Ruben*
Alan P. Safir†
Joan A. Safir†
Edwin C. Scheurer
Michael A. Wiener
Zena Wiener
SCIENTIFIC DIRECTOR
Samuel Waxman, M.D.
ASSOCIATE SCIENTIFIC DIRECTOR
Ethan Dmitrovsky, M.D.
Jonathan Licht, M.D.
SCIENTIFIC ADVISORY COMMITTEE
Franco M. Muggia, M.D.
Frank J. Rauscher III, Ph.D.
I. Bernard Weinstein, Ph.D.
Max S. Wicha, M.D.
Stuart Yuspa, M.D.
EXECUTIVE DIRECTOR
Merle Duskin Kailas
†Chairman Emeriti
*deceased
NEWSLETTER WRITER/EDITOR
Carol Ardman
NEWSLETTER DESIGNER
Barbara Taff
D
r. Max Wicha, a founding
member of the SWCRF
Advisory Committee and
distinguished
cancer
researcher,
recently defended his cancer stem cell
hypothesis in an article published in
the journal of the American Association for Cancer Research. He is committed to this idea, as he is to all the
activities he believes may lead to the
discovery of new approaches and
cures. Borrowing a favorite analogy to
illustrate his belief that breast cancer
stem cells exist and must be targeted,
Photo by Elsa Ruiz
The stem cells are really the root of the plant,
and what we’ve been doing is essentially using
some herbicide that just kills the leaves.
he brings a complex idea down to
was so much opportunity,”he says.“It’s
earth. “The stem cells are really the
turned out to be true. It’s amazing, the
root of the plant, and what we’ve been
increase in our knowledge, particu-
doing is essentially using some herbi-
larly over the last decade.”
cide that just kills the leaves,” he says.
At the same time, he has always
“The roots keep regenerating the
enjoyed being in the clinic.Taking care
plant. If you have two agents to kill the
of patients is important to him. “They
roots and the leaves, you’ll get rid of
have a serious problem and I get to
the cancer faster.”
help them out at a crucial point in
Cancer has been Dr. Wicha’s
their lives,” he revealed. That’s one
abiding interest for much of his career.
reason, he says modestly, that it was a
“I thought research in cancer was
great opportunity to be able to found
going to have the most impact on
the cancer clinic he has headed for the
patients.Treatments were so poor and
past twenty years at the University of
we knew so little about cancer. There
Michigan Cancer Center in Ann Arbor.
3
8th Annual “Collaborating for a Cure” Benefit
Dinner Raises Over $2.8 Million
Our many thanks to the companies and individuals who have made the
“Collaborating for a Cure” Benefit Auction and Dinner such a special event.
ore than 800 people attended our
M
8th annual gala raising a record
$2.8 million. Our evening began
with entertainment by the up-and-coming
band Sam Winch, followed by a sumptuous
Fundraising News
dinner and a live and silent auction. After
dinner, the Counting Crows treated our
guests to an extraordinary performance. The
evening was a powerful display of the energy
and commitment of our supporters as collaborative partners in the search for a cure.
Dr. and Mrs. Samuel Waxman
Charles Schaffran, Meryl Sherman, Kenneth Sherman and Shelly Levine
Janet Lipman, Elin Nierenberg, Julie Assael and Amy Kuriloff
Judi and Gary Gladstein
Steve and Karen Shapiro
David Cantor and David Lavipour
Susan and Gerry Deitchman
Jonathan Licht and Ethan Dmitrovsky,
Associate Scientific Directors
Rebecca Silver, Michael Nierenberg and Kristin Sterling
Michael Nierenberg auctioning Counting Crows’ guitar
Adam Duritz, Counting Crows
Sam Winch
Absolute Asia
Jonathan Adler
Aerosmith
Jeffrey Altman
Antony Todd
Ken Aretsky
Ark Restaurant
The Art of Shaving
Auberge Resorts
Barcelona Restaurant Group
Belle Fleur
Berger's Deli
Penny and Steven Beberman
Big Apple Circus
Bigelow Pharmacy
Bill Blass, Ltd.
Blue Star Jets
The Brandy Library
Sir Richard Branson
Brite Smile
Bruce Brittain
Brody Dermatology
Bryant Park Grill
Bulgari
byRobin
Bryant & Cooper Steakhouse
Canyon Ranch Health Resort
Carnegie Club at Skibo Castle
Cohen’s Fashion Optical
Cookies by Miriam
David Yurman
davidburke & donatella
Harlan DeBell
Jonathan and Karen Duskin
Dynasty Chinese Restaurant
Eleanor Leonard Associates
Ellen Maruca Makeup Salon
Jules Epstein
Equinox
Ken Fish
Jeffrey Fontaigne
Judi Gladstein
Golf Digest
Gramercy Tavern
Alyssa and Cliff Greenberg
Grey Goose
Hal Prince Music
HBO
Dr. Stuart Hershon
David Hinkelman
Bret Hirsh
Hirshleifer’s
Daniel Hoffman
Il Mulino
Il Postino
Isobel O'Neil Studio Workshop
Inn at Palmetto Bluff
Italian Wine Merchants
Jeffrey New York
JimLar
Joan Smith Flowers
Jovia
Joyva Corp.
Just Lauren
The Katz Family
Kayser – Roth Corp.
Kimara Ahnert
Kitchen Kabaret
Steven Kramer
Kramer Photography
Kyros Furs
La Grenouille
La Masseria
Stephen Laffredo
Robin Lathrop
The Laurel Group
Lauren Anne Designs
Scott Lawrence
Le Bernardin/Eric Ripert
Avery Lipman
Longchamp
The Los Angeles Lakers
Magnolia Flowers and Events
Magnum Sand Point Shop
MANE USA
Marc Jacobs
Marie Belle Chocolates
Charles Masson
Masterpiece Printers
Nobu Matsuhisa
Matteo's
MBF Clearing Corp./ Mark Fisher
MD Skincare
Melarosa Florist
Miho Kosuda, Ltd.
Miller Brewing Co.
Myriad Restaurant Group
New Jersey Nets
New York Mets
New York Knicks
New York Yankees
New York City Opera
Elin & Michael Nierenberg
Nobu
Nubest Salon and Spa
Oasis Day Spa
One Model Management/
Scott Lipps
Outback Steakhouse
Palm Restaurant
Paragon Full Service Salon
Party Poopers
Patroon
Marci & Glenn Pere
Philadelphia Flyers
Philadelphia Phillies
Port Beer Distributing Company
Razzanos
Renny and Reed
Restaurant Associates
Revlon, Inc.
Satovsky and Associates
Sephora
Deborah & Howard Shlafmitz
The Shoe Box
Cynthia and Tony Shogren
Showtime
The Silver Family
SKIN
Skip Barber Racing School
Andrew Sloves
Southampton Jewelers
The St. Regis Hotel
Stefans Florist
StoneKelly
Talon Air
Ted Gibson/FAME, Inc.
Katherine Tess
Thirteen/WNET
TLC Meats/ Mim Aronson
Tom James
Transitions
The Tribeca Film Festival
Tribeca Grill
Trish McEvoy Fragrance
Twin Farms
Dr. Michael Tyner
US Mills, Inc.
Uzca
Van Cleef and Arpels
Valerie Wilson Travel
Warner Brothers Records
Marion & Dr. Samuel Waxman
White on White
Debbie and Richard Wilpon
Debra J. Wattenberg
Karen Weinberg
Workman Publishing
Zawacki Dance and Workout
Laurie Zeller
The foundation would like to thank our Event Chairs Elin & Michael Nierenberg and
the Benefit Committee: Penny & Steven Beberman, Dale & Peter Claman, Lauren &
Brad Egna, Carol & Mark Feldman, Judi & Gary Gladstein, Alyssa & Clifford Greenberg, Linda & Dennis Herman, Linda & Gary Jacob, Mary Kantor, Jodi & Marc
Kaplan, Costas Kondylis, Marcia & David Lavipour, Mildred & Abner Levine, Amy &
Thomas Marano, Jill & J. Jay Mautner, Marci & Glenn Pere, Laurie & Charles Schaffran, Deborah & Howard Shlafmitz, Juliette & Larry Silver, Kristin & Clifford Sterling,
Nancy and Craig Overlander
4
Gary and Linda Jacob with Linda and Dennis Herman
Steve Siegel with Joanne and Marc Florin
C. Hugh Hildesley, Auctioneer
Bettina & Spencer Waxman, Dena K. Weiner & David Rozenholc
Event Photos by © Rebecca Weiss Photography
5
Research
News Briefs
Research Progress on
Cancer Dormancy
Milestones
2005
Breast Cancer
Basic Research – Mechanisms
Involved in Cancer
(continued from front cover)
says.“There are lots of possible ways to
with the proper tool kit, may adapt
proceed (with therapies) once one can
(become dormant) and resume growth
reproduce or isolate these cells. And
later instead of dying,” says Dr. Aguirre-
there are lots of questions. One is, if
Ghiso, who is Assistant Professor in the
New Studies on
Cell Survival and Metastasis
there are such tumor stem cells, are
Department of Biomedical Sciences in
Discovery of a switch that allows cancer
cells to become both dormant and
chemotherapy resistant
they marked by the same markers in
the School of Public Health.
preventing them from dividing to form metastases. In 2005,
Dr. Albert Baldwin, University of North Carolina School
studying two proteins – integrin and urokinase – that
of Medicine, reports that cellular factor NF-kappaB, when
interact with one another starting a cascade of events that
activated in many cancers, provides signals for cell survival
Discovery of the hPNPase gene, a regulator of normal and cancer cell differentiation and senescence
leads to cancer cell growth, Dr. Ossowski pinpointed the site
and tumor cell migration and metastasis. His studies indi-
In the University at Albany-SUNY,
make up only about 1%-10% of the
on the urokinase receptor to which the integrin binds, initi-
cate that standard cancer therapies further activate this
NQ01 serves as a gatekeeper for protein
removal, a new cancer specific target
New York, Dr. Julio Aguirre-Ghiso, and
total cells in a breast cancer tumor, may
ating the cascade. Now, using unbiased screening and the
factor, blunting their effectiveness. During the past year Dr.
graduate student Sharon Sequeira are
be relevant to treating it and other can-
collaboration of a computer biologist, 100,000 compounds
Baldwin has shown that one regulatory protein in the NF-
applying their knowledge of a
cers. They have identified a pathway
are being searched for those that can break the bond of
kappaB pathway (IKKkappa) controls growth and survival
pathway discovered to protect head
called NOTCH that these tumor stem
these two proteins.
mechanisms found in many cancers. He is working to
and neck cancers from chemotherapy-
cells need for survival. Within months,
induced killing to breast cancer
using a drug developed by Merck to
Dr. Liliana Ossowski, Mount Sinai School of Medicine, reports
progress on the goal of forcing cancer cells that have spread
from the primary tumor into distant organs into dormancy,
obtain an inhibitor of this pathway to test in models. In
Lung Cancer Clinical Trial for
EGFR Resistant Cells
Report of a set of genes that separates
pre-liver cancer from liver cancer
Pre-Clinical Advances
approximately 10% of non-small cell lung cancers harbor
specific activating mutations within the epidermal growth
factor receptor (EGFR) gene. Lung cancer patients with
EGFR mutations respond rapidly and dramatically to specific EGFR inhibitors Gefitnib (Iressa) and erlotinib (Tarceva).
This has resulted in significant extension of life. However,
relapse can occur due to drug resistance. In Dr. Settleman’s
lab, a distinct class of EGFR inhibitors has been demonstrated to overcome some secondary drug resistance mechanisms in tumors. Clinical trials will soon be conducted with
lung cancer patients who relapsed on Iressa or Tarciva.
All this groundwork is leading to new
started work on that last year.” To
treatments for real people like Sandra.
speed the research, he is also investi-
Dr. Max Wicha and his group at the Uni-
gating ways to shorten the wait for
versity of Michigan were the first to
tumor stem cells to grow in the lab.
show that stemlike cells, though they
clinical trials new compounds are being tested to deter-
Discovery of a novel target for Borte-
studies.They found that normal breast
target these cells, Dr. Wicha and collab-
mine if they work synergistically with chemotherapy or
zomib, useful in treating lymphoma and
cells use this pathway – the endo-
orators will conduct a clinical trial in
radiation in blocking NF-kappaB activation.
breast cancer
plasmic reticulum stress pathway – to
100 patients in Michigan, at the Baylor
trigger death of cells if their surround-
College of Medicine in Texas, and the
ings are not appropriate and to pre-
Dana Farber Center at Harvard.
Report that inhibitors that block NF-kB
enhance the effect of chemotherapy
Dr. Jeffrey Settleman, Harvard University, has shown that
different tumors of the same type? We
Understanding Drug Interaction
and Tumor Suppression
Yosef Shaul, Weizmann Institute of Science, reports that his
vent uncontrolled growth. But in Dr.
“For years Sam Waxman has been
Aguirre-Ghiso’s lab, some breast
talking about differentiation therapy,”
Discovery that arsenic trioxide may be effec-
cancer cells use this pathway to
says Dr. Wicha.“Now a variation of that
tive in treating other forms of leukemia and
become dormant instead of dying.
is exactly what we need for some stem
and radiation
myelodysplastic syndrome
“You can draw a very long parallel to
cells. One reason we can’t kill them is
nature. Sometimes when plant seeds
they don’t differentiate normally into
aren’t in proper soil or are nutrient
other cells that lose the self-renewing
deprived, they may die or remain dor-
properties. If we could make the stem
Clinical Advances
mant for years and then germinate.
cells differentiate, we could prevent
Current chemotherapy induces stress
the cancers altogether.”
Discovery of a new distinct class of EGFR
in cancer cells and those equipped
lab has discovered a protein degradation pathway that is
amenable to pharmacological manipulation. In this
pathway, certain proteins are degraded “by default” by cellular degradation complexes called the 20S proteasomes.
Some proteins degraded by this pathway are directly relevant to cancer, such as tumor suppressor protein p53.
Another protein, NQ01, associates with 20S proteasomes,
Discovery of inhibitors that selectively kill
melanoma cells with the B-Raf mutation
It’s just a question of time.
inhibitors effective in lung cancer
binds to and protects proteins from degradation. DegradaDemonstration that combining arsenic
Scientific Director’s Message
NQO1; protein levels can also be raised with drugs that
with Gleevac is effective in treating the
(continued from page 2)
increase expression of NQ01. The lab is currently working
aggressive phase of chronic myeloge-
abnormal differentiation and contribute to the development of breast cancer. In addi-
toward deeper understanding of this system.
nous leukemia
tion,other gene expressions unique to breast cancer are being studied for the purpose
tion of a protein can be induced with drugs that inhibit
of developing therapies specific to this serious medical problem. Our investigations
6
(If you would like more information on
into breast cancer also relate to other forms of cancer, since we are examining mecha-
these published articles, please contact
nisms which characterize cancer cells in general. Thus, the SWCRF has a well-coordi-
us at: [email protected])
nated, collaborative breast cancer program. With your help our work will continue to
grow in scope and discovery. – Samuel Waxman
7
HOLD THE DATES: Special Events Calendar 2006
Monday, May 22nd, 2006
Monday, October 23rd, 2006
24th Annual Golf Tournament
Brae Burn Country Club
David T. Workman
Memorial Award Ceremony
Come win the $1 Million prize for a “hole in one”
New York Yacht Club
Saturday, July 8th, 2006
Thursday, November 30th, 2006
3rd Annual Hamptons Happening
Gourmet Tasting Stations
and Silent Art Auction
“Collaborating for a Cure”
Benefit Dinner
Silent and Live Auction
On Georgica Pond, Wainscott
Help us keep costs down, please send your email address to [email protected]
PERMIT NO. 938
www.waxmancancer.org
Tel: 212-241-1760 Fax: 212-426-2273
1150 Fifth Avenue, New York, NY 10128
Samuel Waxman
Cancer Research Foundation
NEW YORK, NY
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