2 From the Chairman & Scientific Director

3 Research Highlights

4 Fundraising Events

6 News Briefs

8 Special Events Calendar

Samuel Waxman Cancer Research Foundat ion

I n s i d e

REP RT Spring 2006

A t the age of thirty-six, a friend we’ll call

Sandra needed a lumpectomy and radia-

tion for breast cancer. Her recovery was

uneventful; she called her cancer “a thing of the past.”

That was twenty-three years ago. Recently, a recur-

rence necessitated a mastectomy. This time Sandra’s

recovery has been difficult, and now her doctors are

“discouraged.” Unfortunately, her story is familiar.

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

Medical Center in Boston is investigating the idea that

a small population of cells is responsible for tumor for-

mation. 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

Breast Cancer-Killing The Last Cell

cells can produce a whole new tumor.

“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

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,

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

can grow back with more mutations which make it

more difficult to kill.”

Dr. Neel and his colleagues are trying to demon-

strate that what has been learned about tumor hier-

archy in research on leukemias also applies to breast

cancer. Both mouse and human models are helping

him and his coworkers toward that goal, and to

develop ideas about how to target tumor stem cells

selectively, with drugs. “The ultimate goal is to use

biopsy to identify tumor stem cells and determine

their self-renewal and survival characteristics,”Dr. Neel

(continued on page 7)

TUMOR CELL CANCER STEM CELL

1. Original tumor 2. After treatment 3. Tumor regrows

1. Original tumor 2. After treatment 3. Tumor shrinks,no regrowth

UNDERSTANDING STEM CELLS AND DIFFERENTIATION

But, if treatment can be tailored to differentiate and killcancer stem cells, they may destroy the tumor permanently.

Illu

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Source: Science News

32

From the Chairman & Scientific DirectorMichael Nierenberg

Dear Friends,

2006 is off to an incredible start!

Our “Collaborating for a Cure” Benefit

raised a record breaking $2.8 million.

Because of your generosity we continue

to fund vital research programs all over

the world so that one day our children

can live in a world without cancer.

As you will read in News Briefs and

Milestones, we’ve made significant

progress in treating leukemia and other

forms of blood malignancies. We also

report on two breakthroughs in science:

new and specific treatments of mel-

anoma and lung cancer and basic research

in breast cancer stem cells which will

result in saving more lives in the not-so-

distant future.

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 impor-

tantly, 85% of all funds raised will go

directly into cancer research.

To sustain this level of activity and ded-

Y es, we are winning in the battle to

defeat breast cancer. Although more

women will get breast cancer, better edu-

cation leading to earlier diagnosis and

coordinated treatment by surgeons, med-

ical and radiation oncologists and genetic

advisors is leading to a higher cure rate and

a decrease in mortality. This achievement

has required billions of dollars, worldwide

innovative research, government commit-

ment and women’s advocacy pressure.

How then does a small foundation such

as SWCRF contribute to this massive com-

mitment to beat breast cancer?

As you will read in this newsletter, the

SWCRF is focusing on the tragedy of late

recurrence of breast cancer due to dormant

and cancer stem cells. Dormant cancer cells

are difficult to detect, treat and can revert to

aggressive growing tumor-forming cells.

SWCRF scientists have found a specific

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

Samuel Waxman, M.D.

OFFICERS OF THE BOARD

CHAIRMANMichael Nierenberg

VICE-PRESIDENTSGary Jacob

J. Jay MautnerDena K. Weiner

SECRETARYLaurie L. Schaffran

TREASURERGary Gladstein

BOARD OF DIRECTORSLawrence AltmanPhilip T. Brudner

Peter ClamanRobert E. Fischer

Arminio FragaJudi GladsteinEric Goldstein

Clifford GreenbergLinda HermanMary Kantor

Costas KondylisLeslie Elliot Krause

Abner LevineMildred Levine

Shumer S. Lonoff*Thomas MaranoRichard Mazer

Alfred J. Seaman†

Edward SheldonHoward ShlafmitzTony M. ShogrenClifford Sterling

Spencer WaxmanDavid T. Workman*†

HONORARY BOARDMaureen CoganMartin L. CoyneSusan W. RoseSelma Ruben*Alan P. Safir†

Joan A. Safir†

Edwin C. ScheurerMichael A. Wiener

Zena Wiener

SCIENTIFIC DIRECTORSamuel Waxman, M.D.

ASSOCIATE SCIENTIFIC DIRECTOREthan Dmitrovsky, M.D.

Jonathan Licht, M.D.

SCIENTIFIC ADVISORY COMMITTEEFranco 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 DIRECTORMerle Duskin Kailas

†Chairman Emeriti*deceased

NEWSLETTER WRITER/EDITORCarol Ardman

NEWSLETTER DESIGNERBarbara Taff

samuel waxman

c ancer research

foundat ion

Research Highlights

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 Associa-

tion for Cancer Research. He is com-

mitted 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,

he brings a complex idea down to

earth. “The stem cells are really the

root of the plant, and what we’ve been

doing is essentially using some herbi-

cide that just kills the leaves,” he says.

“The roots keep regenerating the

plant. If you have two agents to kill the

roots and the leaves, you’ll get rid of

the cancer faster.”

Cancer has been Dr. Wicha’s

abiding interest for much of his career.

“I thought research in cancer was

going to have the most impact on

patients.Treatments were so poor and

we knew so little about cancer. There

ication to our mission, Dr. Ethan Dmitro-

vsky has joined Dr. Jonathan Licht as Asso-

ciate Scientific Director. Dr. Dmitrovsky is

the Andrew G. Wallace professor at Dart-

mouth Medical School, and the Chairman

of the Department of Pharmacology and

Toxicology. He also serves as a member of

the Lance Armstrong Foundation Scien-

tific Advisory Board.

By this time next year, our

researchers will be able to log on to a

secure site and share their latest findings.

What makes our Foundation unique is its

insistence that our researchers collabo-

rate. As grants are awarded only upon

proof of this collaboration, this site will

bring us to a new level of greatly

enhanced communication.

To add to this year’s excitement, we

have just hired a new Director of Devel-

opment, Mark Silverstein. He joins us with

15 years of solid fundraising experience,

most recently with The Skin Cancer Foun-

dation 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 enor-

mously grateful.

– Michael Nierenberg

Max Wicha, Committed Cancer Sleuth

was so much opportunity,”he says.“It’s

turned out to be true. It’s amazing, the

increase in our knowledge, particu-

larly over the last decade.”

At the same time, he has always

enjoyed being in the clinic.Taking care

of patients is important to him. “They

have a serious problem and I get to

help them out at a crucial point in

their lives,” he revealed. That’s one

reason, he says modestly, that it was a

great opportunity to be able to found

the cancer clinic he has headed for the

past twenty years at the University of

Michigan Cancer Center in Ann Arbor.

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.

Photo by Elsa Ruiz

(continued on page 7)

85% of all funds raised will go directly into cancer research.

4

More than 800 people attended our

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

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 collab-

orative partners in the search for a cure.

8th Annual “Collaborating for a Cure” Benefit

Dr. and Mrs. Samuel Waxman

Fund

raisi

ng N

ews

Dinner Raises Over $2.8 Million

Judi and Gary Gladstein

Absolute AsiaJonathan AdlerAerosmithJeffrey AltmanAntony ToddKen AretskyArk RestaurantThe Art of ShavingAuberge ResortsBarcelona Restaurant GroupBelle FleurBerger's DeliPenny and Steven BebermanBig Apple CircusBigelow PharmacyBill Blass, Ltd.Blue Star JetsThe Brandy LibrarySir Richard BransonBrite SmileBruce BrittainBrody DermatologyBryant Park GrillBulgaribyRobinBryant & Cooper SteakhouseCanyon Ranch Health ResortCarnegie Club at Skibo CastleCohen’s Fashion OpticalCookies by MiriamDavid Yurmandavidburke & donatellaHarlan DeBellJonathan and Karen DuskinDynasty Chinese RestaurantEleanor Leonard Associates

Ellen Maruca Makeup SalonJules EpsteinEquinoxKen FishJeffrey FontaigneJudi Gladstein

Golf DigestGramercy TavernAlyssa and Cliff Greenberg Grey GooseHal Prince MusicHBODr. Stuart HershonDavid HinkelmanBret HirshHirshleifer’sDaniel HoffmanIl MulinoIl PostinoIsobel O'Neil Studio WorkshopInn at Palmetto BluffItalian Wine MerchantsJeffrey New YorkJimLarJoan Smith FlowersJoviaJoyva Corp.Just LaurenThe Katz FamilyKayser – Roth Corp.Kimara AhnertKitchen KabaretSteven KramerKramer PhotographyKyros FursLa GrenouilleLa MasseriaStephen LaffredoRobin LathropThe Laurel GroupLauren Anne DesignsScott LawrenceLe Bernardin/Eric RipertAvery LipmanLongchampThe Los Angeles LakersMagnolia Flowers and EventsMagnum Sand Point ShopMANE USAMarc JacobsMarie Belle ChocolatesCharles MassonMasterpiece PrintersNobu MatsuhisaMatteo'sMBF Clearing Corp./ Mark FisherMD SkincareMelarosa FloristMiho Kosuda, Ltd.Miller Brewing Co.Myriad Restaurant GroupNew Jersey NetsNew York MetsNew York KnicksNew York Yankees

New York City OperaElin & Michael NierenbergNobuNubest Salon and SpaOasis Day Spa One Model Management/

Scott LippsOutback SteakhousePalm RestaurantParagon Full Service SalonParty PoopersPatroonMarci & Glenn PerePhiladelphia FlyersPhiladelphia PhilliesPort Beer Distributing CompanyRazzanosRenny and ReedRestaurant AssociatesRevlon, Inc.Satovsky and AssociatesSephoraDeborah & Howard ShlafmitzThe Shoe BoxCynthia and Tony ShogrenShowtimeThe Silver FamilySKINSkip Barber Racing SchoolAndrew SlovesSouthampton JewelersThe St. Regis HotelStefans FloristStoneKellyTalon AirTed Gibson/FAME, Inc.Katherine TessThirteen/WNETTLC Meats/ Mim AronsonTom JamesTransitionsThe Tribeca Film FestivalTribeca GrillTrish McEvoy FragranceTwin FarmsDr. Michael TynerUS Mills, Inc.UzcaVan Cleef and ArpelsValerie Wilson TravelWarner Brothers RecordsMarion & Dr. Samuel WaxmanWhite on WhiteDebbie and Richard WilponDebra J. WattenbergKaren WeinbergWorkman PublishingZawacki Dance and WorkoutLaurie Zeller

Our many thanks to the companies and individuals who have made the“Collaborating for a Cure” Benefit Auction and Dinner such a special event.

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 Green-

berg, 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 Schaf-

fran, Deborah & Howard Shlafmitz, Juliette & Larry Silver, Kristin & Clifford Sterling,

Bettina & Spencer Waxman, Dena K. Weiner & David Rozenholc 5

Susan and Gerry Deitchman Michael Nierenberg auctioning Counting Crows’ guitar

Steve and Karen Shapiro Adam Duritz, Counting Crows

Sam Winch

Charles Schaffran, Meryl Sherman, Kenneth Sherman and Shelly Levine Jonathan Licht and Ethan Dmitrovsky,

Associate Scientific Directors

Janet Lipman, Elin Nierenberg, Julie Assael and Amy Kuriloff Rebecca Silver, Michael Nierenberg and Kristin SterlingDavid Cantor and David Lavipour

Gary and Linda Jacob with Linda and Dennis Herman

Steve Siegel with Joanne and Marc FlorinNancy and Craig Overlander C. Hugh Hildesley, Auctioneer

Event Photos by © Rebecca Weiss Photography

6 7

(continued from front cover)Breast Cancer

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,

preventing them from dividing to form metastases. In 2005,

studying two proteins – integrin and urokinase – that

interact with one another starting a cascade of events that

leads to cancer cell growth, Dr. Ossowski pinpointed the site

on the urokinase receptor to which the integrin binds, initi-

ating the cascade. Now, using unbiased screening and the

collaboration of a computer biologist, 100,000 compounds

are being searched for those that can break the bond of

these two proteins.

Dr. Jeffrey Settleman, Harvard University, has shown that

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 spe-

cific 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 demon-

strated to overcome some secondary drug resistance mech-

anisms in tumors. Clinical trials will soon be conducted with

lung cancer patients who relapsed on Iressa or Tarciva.

News Briefs

Dr. Albert Baldwin, University of North Carolina School

of Medicine, reports that cellular factor NF-kappaB, when

activated in many cancers, provides signals for cell survival

and tumor cell migration and metastasis. His studies indi-

cate that standard cancer therapies further activate this

factor, blunting their effectiveness. During the past year Dr.

Baldwin has shown that one regulatory protein in the NF-

kappaB pathway (IKKkappa) controls growth and survival

mechanisms found in many cancers. He is working to

obtain an inhibitor of this pathway to test in models. In

clinical trials new compounds are being tested to deter-

mine if they work synergistically with chemotherapy or

radiation in blocking NF-kappaB activation.

Yosef Shaul, Weizmann Institute of Science, reports that his

lab has discovered a protein degradation pathway that is

amenable to pharmacological manipulation. In this

pathway, certain proteins are degraded “by default” by cel-

lular degradation complexes called the 20S proteasomes.

Some proteins degraded by this pathway are directly rele-

vant to cancer, such as tumor suppressor protein p53.

Another protein, NQ01, associates with 20S proteasomes,

binds to and protects proteins from degradation. Degrada-

tion of a protein can be induced with drugs that inhibit

NQO1; protein levels can also be raised with drugs that

increase expression of NQ01. The lab is currently working

toward deeper understanding of this system.

Research Progress on Cancer Dormancy

Lung Cancer Clinical Trial forEGFR Resistant Cells

New Studies on Cell Survival and Metastasis

Understanding Drug Interactionand Tumor Suppression

says.“There are lots of possible ways to

proceed (with therapies) once one can

reproduce or isolate these cells. And

there are lots of questions. One is, if

there are such tumor stem cells, are

they marked by the same markers in

different tumors of the same type? We

started work on that last year.” To

speed the research, he is also investi-

gating ways to shorten the wait for

tumor stem cells to grow in the lab.

In the University at Albany-SUNY,

New York, Dr. Julio Aguirre-Ghiso, and

graduate student Sharon Sequeira are

applying their knowledge of a

pathway discovered to protect head

and neck cancers from chemotherapy-

induced killing to breast cancer

studies.They found that normal breast

cells use this pathway – the endo-

plasmic reticulum stress pathway – to

trigger death of cells if their surround-

ings are not appropriate and to pre-

vent uncontrolled growth. But in Dr.

Aguirre-Ghiso’s lab, some breast

cancer cells use this pathway to

become dormant instead of dying.

“You can draw a very long parallel to

nature. Sometimes when plant seeds

aren’t in proper soil or are nutrient

deprived, they may die or remain dor-

mant for years and then germinate.

Current chemotherapy induces stress

in cancer cells and those equipped

with the proper tool kit, may adapt

(become dormant) and resume growth

later instead of dying,” says Dr. Aguirre-

Ghiso, who is Assistant Professor in the

Department of Biomedical Sciences in

the School of Public Health.

All this groundwork is leading to new

treatments for real people like Sandra.

Dr. Max Wicha and his group at the Uni-

versity of Michigan were the first to

show that stemlike cells, though they

make up only about 1%-10% of the

total cells in a breast cancer tumor, may

be relevant to treating it and other can-

cers. They have identified a pathway

called NOTCH that these tumor stem

cells need for survival. Within months,

using a drug developed by Merck to

target these cells, Dr. Wicha and collab-

orators will conduct a clinical trial in

100 patients in Michigan, at the Baylor

College of Medicine in Texas, and the

Dana Farber Center at Harvard.

“For years Sam Waxman has been

talking about differentiation therapy,”

says Dr. Wicha.“Now a variation of that

is exactly what we need for some stem

cells. One reason we can’t kill them is

they don’t differentiate normally into

other cells that lose the self-renewing

properties. If we could make the stem

cells differentiate, we could prevent

the cancers altogether.”

It’s just a question of time.

Research Milestones2005Basic Research – Mechanisms Involved in Cancer

Discovery of a switch that allows cancer

cells to become both dormant and

chemotherapy resistant

Discovery of the hPNPase gene, a regu-

lator of normal and cancer cell differen-

tiation and senescence

NQ01 serves as a gatekeeper for protein

removal, a new cancer specific target

Report of a set of genes that separates

pre-liver cancer from liver cancer

Pre-Clinical Advances

Discovery of a novel target for Borte-

zomib, useful in treating lymphoma and

breast cancer

Report that inhibitors that block NF-kB

enhance the effect of chemotherapy

and radiation

Discovery that arsenic trioxide may be effec-

tive in treating other forms of leukemia and

myelodysplastic syndrome

Discovery of inhibitors that selectively kill

melanoma cells with the B-Raf mutation

Clinical Advances

Discovery of a new distinct class of EGFR

inhibitors effective in lung cancer

Demonstration that combining arsenic

with Gleevac is effective in treating the

aggressive phase of chronic myeloge-

nous leukemia

(If you would like more information on

these published articles, please contact

us at: SWCRF@waxmancancer.org)

abnormal differentiation and contribute to the development of breast cancer. In addi-

tion,other gene expressions unique to breast cancer are being studied for the purpose

of developing therapies specific to this serious medical problem. Our investigations

into breast cancer also relate to other forms of cancer, since we are examining mecha-

nisms which characterize cancer cells in general. Thus, the SWCRF has a well-coordi-

nated, collaborative breast cancer program. With your help our work will continue to

grow in scope and discovery. – Samuel Waxman

(continued from page 2)

Scientific Director’s Message

Samuel Waxman

Cancer ResearchFoundation

Help us keep costs down,please send your email address to report@waxmancancer.org

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www.waxmancancer.org

Thursday, November 30th, 2006

“Collaborating for a Cure”Benefit Dinner Silent and Live Auction

Saturday, July 8th, 2006

3rd Annual Hamptons HappeningGourmet Tasting Stations and Silent Art Auction

On Georgica Pond, Wainscott

Monday, October 23rd, 2006

David T. Workman Memorial Award CeremonyNew York Yacht Club

Monday, May 22nd, 2006

24th Annual Golf TournamentBrae Burn Country Club

Come win the $1 Million prize for a “hole in one”

HOLD THE DATES: Special Events Calendar 2006