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April 15, 1996Volume 5ó•Number 8PP.1707-1959ISSN0008-5472 •CNREA 8

3rd International Symposium •PlenaryProgram•http: //www.Ummed.edU:8000/dE)t/canCerprev

Detailsfrom: HENieburgsMD•Fax:508-856-1824@ Tel:212-534-4991•e-mail:cu@caOw@.umm.d.eduCorrespondence: Box 20, Universityof MassachusettsMedicalCentei@55 LakeAve N, Worcester,MA 01655 USA

Sponsorsdbythshi@nistondSodsiyhrPami@teOncdogymol@dsImIstouWiI@ThWOMHSI@IOVgntZntSIUmdThS@st@AsiicykrRsusmhonC@, andccspo.isorsdby11.Fie@thNston@ @@C@im@Cawhhli@i@@ (MiSSntIYOIPICSSspIà-Ai@cIh MS@cII,Th.I@INstm@ PSAQSinItC@ar,

N@ion@hI@ICrftNSrdI onC@@ Ad@,ed Shi@hgyC@ (Gssioal,IMiVUrIi'YC&@IOiIC@SdMSdIdnS ffhbona@UnUn5ydMamthUNINI@diC@CSI@Ur @Oam@),MOS.OdWISItISiolsclmohajCouid

@kLGE !‘@!@ t$T iSP• 0@ Z@ L@IGR

MultiplegenemutationsDNA repair deficienciesAR SARASIN, PhD

CNRSCancerResearch,Villejuif

Angiogenesis inhibitorsRMONIER,PhD RSKERBEL.PhD

Gustav. Roussy,ViI.jtM SunnybrookHSC,Toronto

Molecular screeningmodalities I MANDEL,PhD

UnivMinnesota,Minneapolis

DNA adduct levelsSA KYRTOPOULOS,@

National Hellenic Fndn, Athens

Telomeraseprognosisis siip@y,PhD

Southwestern Med Ctr@Dallas

Glycobiology of metastasisK OLDEN,PhD

NIEHS,ResTrianglePark,NC

Growth factor receptorsPCOMOGIJO, MD,PhD

UnivTurin,Turin,Italy

Signal transductionlB WEINSTEIN,@

Columbia Univ Cancer Cfr, NY

Chronic oxidative stressLA LOEB,MDPhD

UnivWashington,Seattle

Genomic instabilityCRBOLAND,MD

UnivCalifornia, SanDiego

Cell transformation byoncogenic refroviruses

I CHIECO BIANCHI, MDUniv Padua,Paclua,Italy

Cell cyclecontrol& differentiation

Molecular geneticsL STRONG,MD

(JIXMDMdsrson CancrCh@Houston

CarcinogenicsusceptibilityS PARODI,MDPhD

NaIionaICanc@R.s.ardt Ch@Geaco

PrecursorlesionsEDMRROVSKY,MD

Memorial Sloan-K.tt.ring Or, NY

Biomarkersof carcinogenexposure RsANmu.A,@

ColumbiaUnivCon@ Ch@NY

Managementpatientsat risk. i HORTON, MIO@

MoffittCanc@Ctr@Tampa

I @k@X@iSystemicmarkers

KFRENKEL,PhDNYU,NY

Site-specificmarkersWR BRUCE,MDPhD

Onto@ Cancerku@Toronto

Preneoplaslicp53 expressionG SELIVANOVA,@

Kcrolk@katos@$$oddi@m

Prognosticimplications ofheat shock proteins

SFUQUA,PhDIJTX,SanAntonio

DNA adductsofcarcinogen exposure

CWILD,PhD@RC,Lyon

Prognosticoncogeneexpression zRONAI,

Am.rkon HealthFncln,VaLolla, NY

Genetically engineeredvaccines CLOCHT,MD

InstitutPasteur,111k

Reversalof drug resistancePW1ERNIK,MD

A EinsteinMed Ch@Bronx, NY

AntisensetherapyAM GEW1RTZ, MD

Univ Pennsylvania,Philadelphia

Bridging researchto clinicRA GOOD, MDPhD

UnivSFlorida,StPetersburg

Molecular geneticslymphoid neoplasms

U JAEGER,MDAilgermeinesKrankenhaus,Vienna

Choiceof gene therapyvectors RCRISTIANO,MD

MIX MD AndersonCancerCtr@Houston

Stemcell delivery systemsp QUESENBERRY,MD

Univ Massachusetts,Worcester

Refroviral gene therapyAB DEISSEROTH,MDPhDYaleCancerOr, New Haven

Adenoviral gene transferM PERRICAUDET,PhDGustaveRoussy,Villejuif

Clinicaluseof growth factorsI GABRILOVE,MD

Memorial SloanKetteringCh@NY

Earlydetection& therapyV KOROLTCHOUK,MD

WHO, Geneva

pHINDS,MDHarvard Med School,Boston

Oncogene& tumorsuppressorgene mutations

M GREENBLA1T,MDUnivWrmont Med College,Burlington

Transgenicmousemodelsfor tumor suppressorgenes

MM MATZUK,MDPhDBaylorCOllegeMed. Houston

@E@@D©TOYE@©@C©@©@Vc@@

IMPACTOFCANCERBIOTECHNOLOGYDIAGNOSTIC& PROGNOSTICINDICATORS

Nice, France •October 26-28,1996

Hans@OIovAdamiI Uppsala,SwedenJ. CarlBarreftI ResearchmanglePark,USAPaoloBoffettaI Lyon,FranceEdwardBresnickI Worcester,USAMieczyslawR.Chor@zyI Gliwice,PolandJosephF. Fraumeni,Jr. / Bethesda,USA

WaunKi HongI Houston,USAMargaretL Kripke/ Houston,USAKennethOldenI ResearchTrianglePark,USAAlanPintérI Budapest,HungaryManfredF.Rajewsky/ Essen,GermanyDavidZaridze/ Moscow,Russia

SCIENTIFIC PROGRAM

KeynoteAddressCurtisC.HarrisI Bethesda,USA

CancerIncidenceand EtiologyWitoldA.ZatoñsklI Warsaw,PolandFredericaPereraI NewYork,USAJ.CarlBarrettI ResearchmanglePark,USAHelmutBartschI Heidelberg,Germany

Air,Water,Food,andSoilContaminationRadlmJ. @rámI Prague,CzechRepublicJoellenLewtasI ResearchTrianglePark,USAWieslawJedrychowsklI Cracow,PolandOlavAxelsonI LinkOping,Sweden

Ambient,Environmental,andOccupationExposureandCancerRiskMieczyslawR.Chor@±yI Gliwice,PolandAlanPintérI Budapest,HungaryKlmmoPeltonenI Helsinki,FinlandMonicaC.HollsteinI Heidelberg,GermanyKarlHemmlnklI Stockholm,Sweden

TobaccoIvanPlesko/ Bratislava,SlovakiaBarbaraS.HulkaI ChapelHill,USAPaoloL VinelsI Turin,ItalyStephenS.HechtI Valhalla,USAKrystynaFrenkelI NewYork,USABernadetteSchoketI Budapest,Hungary

Strategiesfor PreventionWaunKi HongI Houston,USAI.BernardWeinsteinI NewYork,USAAnnaTompaI Budapest,Hungary

RoundtableDiscussionPaulKleihuesI Lyon,FranceHans•OlovAdamiI Uppsala,SwedenPaoloBoffettaI Lyon,FranceEdwardBresnickI Worcester,USAAndrewE.CzeizelI Budapest,HungaryTernDamstraI ResearchTrianglePark,USAEdithOlahI Budapest,HungaryKennethOldenI ResearchTrianglePark,USAManfredF. RajewskyI Essen, GermanyWilliamA.SukI ResearchTrianglePark,USADavidZaridzeI Moscow,Russia

Applicants are encouraged to submit abstractsfor poster presentation.

Information and Application Forms

AmericanAssociationfor CancerResearchPublicLedgerBuilding,Suite816150S. IndependenceMallWestPhiladelphia,PA 19106-3483(215) 440-9300 (215) 440-9313 (FAX)Email:aacr@aol.com

CARCINOGENESIS FROM ENVIRONMENTALPOLLUTION: ASSESSMENT OF HUMAN RISK

AND STRATEGIES FOR PREVENTION

Joint MeetingOrganized by theAmerican Associationfor Cancer Research(AACR)

and the InternationalAgency for Researchon Cancer (IARC)

With the Collaboration of the Hungarian Cancer Society

October 6-9, 1996Hotel Gellért

Budapest,Hungary

CONFERENCE CHAIRPERSONSFredericaPereraINewYork,USAPaulKleihuesILyon,France

PROGRAM COMMITTEE

MAYO CLINICDIVISION OF MEDICAL ONCOLOGY

AND MAYO CANCER CENTERClinical Research Positions

The Division of Medical Oncology and the NCI-designatedMayo Cancer Center in Rochester, Minnesota, invite applications for two clinical researchpositions.Clinical investigatorswith establishedcancerresearchprogramsare encouragedtoapply. The Mayo Clinic provides an outstanding environmentfor investigators interested in conducting translational researchwith the goal of improving prevention,diagnosis,and treatmentof cancer.Interestedapplicantsshouldsubmitastatementof researchinterests,curriculumvitae,bibliography,andlist ofreferencesto:

James N. Ingle, M.D.Associate Director for Clinical Research

Mayo CancerCenterMayo Clinic

200 First Street, SWRochester,MN 55905

Mayo Foundation is an affirmative action and equalopportunity educator and employer.

THE SURGERY BRANCH, NATIONAL CANCER INSTITUTE, NIH, IS SEEKING PATIENTS FORONGOING CLINICAL TREATMENT PROGRAMS.

PATIENTS WITH THE FOLLOWING MALIGNANCIES ARE BEING TREATED UNDER COMBINEDMODALITY OR INNOVATIVE IMMUNOTHERAPY PROGRAMS:

•METASTATIC MELANOMA AND KIDNEY CANCER •

•STAGE II OR LOCALLY ADVANCED BREAST CANCER •

•METASTATIC COLORECTAL CANCER TO THE LIVER •

•LOCOREGIONAL GASTRIC OR PANCREATIC CANCER •

•MESOTHELIOMA, PULMONARY METASTASES, STAGE lIlA, B LUNG CANCER

OR ESOPHAGEAL CANCER •

•LOCALIZED SOFT TISSUE SARCOMAS •

•PERITONEAL CARCINOMATOSIS.

CARE FOR ALL PATIENTS IS PROVIDED AT THE CLINICAL CENTER, NIH,BETHESDA, MARYLAND.

FOR MORE INFORMATION ON CANCER PROGRAMS, PLEASE CALL(301) 496-1533

A PuBLIcSERVICEANNOUNCEMENTCOURTESYOFTHISPUBLICAT1ON

Texas Tech UniversityHealth Sciences Center

A Post-Doctoral Position is availableimmediately to study drug resistanceand cancer. Candidate should have aPh.D. or M.D. degree with backgroundin drug resistance and molecular biology. Good salary, excellent working environment. Send curriculum vitae to:

Maria ClaudiaMallarino, M.D.Texas Tech University Health Sciences Center

Oncology Division

Department of Internal Medicine

3601 4th Street

Lubbock, Texas 79430

Phone:(806)743-3155;Fax:(806)743-3148

NW1ONALI ( ANGER

INSTITUTE

birth to 19 years of age decreased38.4%; from 20 to 44 years, 20.7%; and from45 to 54 years, 10.5%. This is terrific news for young people who earlier wouldhave had a fatal diagnosis if told they had leukemia, Hodgkin's disease, ortesticular cancer. Today they can survive these previously devastating tumorsthanks to the hard-won victories achieved primarily through federally supportedmedical research.A 17-year government investment of a total of $56 million intesticular cancer research yielded a 91% cure rate, with an increased life expectancy of 40 yearsand a savings of $166 million annually. This was a great benefitto the patientsand a big bargain for the taxpayers.This type ofvictory is our proofof principle, but we have not yet won on the major fronts. Most of the cancersinAmerica occur in the lung, colon, breast,and prostate,and the incidence, mortality,and cost of these cancers are steadily increasing. Unless these cellular foes arehalted by progressin research,they will continue to drive the suffering, death,andcost from cancer to an unprecedentedlevel. In fact, by the turn of the century,cancer is expected to be the Nation's #1 killer.

The research community cannot afford to be silent any longer. We must allbe active leaders; let us draw up new battle plans. These must include: politicalcampaigns, scientific campaigns, financial campaigns, industrial campaigns,media campaigns, whatever it takes. Let us focus on funding, which is alwaysso critical to any campaign. The fiscal realities must be considered in thesetimes of spending constraints. Today, cancer health care costs the Americanpeople $104 billion per year, a level that is over SOtimes the NCI budget. Putanother way, the NCI budget to help reduce this disease is equivalent to only2% of this annual cancer health care cost. Any discovery that impacts cancerquickly returns the investment, and this does not even take into considerationreducing the potential for human suffering and personal loss due to cancer.

How can we restore our spirits? Even with the limited number of investigators and inadequate support, cancer researchers can take pride in the largenumber of new and exciting discoveries that they have generated since thepassageof the National Cancer Act of 1971. Among those contributing to themany advances in the field have been the distinguished recipients of the AACRawards. The names of the award winners from 1971—1996appear on the frontcover below a list of some of the major discoveries and areasof activity in thefieldoverthepast25years.Eachdaytheseandotherdiscoveriesareilluminating our battlefield and are placing the cancer targets into sharper focus.

Are we short of questions that, if studied, might yield surprising new ideasand insights? Absolutely not. We all have favorite research questions we wishsome young scientist would pursue and solve. A few of my own favorites are:(a.) Why is prostate cancer so common in the human and dog and yet totallyabsent from all other animal species such ascats, bulls, and horses?What is themolecular mechanism that protects these species? (b.) Why are some organs inthe human totally resistant to developing cancers? For example, the seminalvesicles, epididymis, and bulbourethral gland are devoid of tumors, eventhough they share the same genes. (c.) Why does an inherited cancer mutationremain silent in some cells but highly active in others? How does the samegene yield different proteins in different cells? (d.) What sets and determinesthe exquisite balance in the rates of cell gain and cell loss in our normalorgans? Other investigators have even better and more timely questions in theirown areas.

Today, there are a tremendous number of good ideas at both the clinical andbasic levels that are not being studied. We urgently need a balanced attack ofa much higher magnitude than is now available. The last five types of cancercured came from both great clinical and great basic research; neither area ofresearch has greater importance, nor should it have when it comes to funding.

What is on the immediate horizon? There are hundreds of good leads thatcannot be followed today because of limited funds. The chances for fundingkeep getting worse. The overall percentage of approved but unfundedinvestigator-initiated grants steadily increased from 40% in the l970s to 85%in 1995. We are hopeful that it will come down to only 75% in 1996. If thePresident's 1997 budget request for the NC! is approved, still about 3 out of 4of all NC! research grants that have been approved following scientific peerreview will lie silent and inactive without funding. This continues to representlost opportunities in our important mission. To turn this trend around weourselves must act first and then recruit help from a variety of sectors, fromleaders in the community, and from the public at large.

As President Nixon stated when he signed the National Cancer Act almost25 years ago on December 23, 1971, it is essential to have “.. . a totalcommitment of Congress and the President . . . to provide the funds . . . for theconquest of cancer.―This legislation was a contract with America that everypatient, researcher, and potential victim is waiting to celebrate one day with agreat sigh of relief. Cancer must and will be conquered. Whether it be throughprevention, control, or cure, it will be accomplished by good, well-fundedresearch. It is past the time to declare the real World War I! on cancer. Justreading this won't make a hill of beans difference if we don't all get up and dosomething about it, both as individuals and as a society. Godspeed in yourefforts.

Donald S. CoffeyPresident-Elect, 1996—97American Association for

Cancer Research

I I ( ulgersilig $iII,(IIIi1,.'.

COVER LEGEND. April 15, 1996

CancerResearch

Marking the 25th Anniversary of the National Cancer Act:A New Call to Arms

In 1971 the U.S. Government declared war on cancer, but the term has beena great misnomer and has led to false expectations by everyone. Visualizing thetight against cancer as a war is an appropriate analogy, but the battle with thisenemy is too often left to defenseless patients, and their casualties are unacceptable to all of us. To win this war, we desperately need new, modernweapons that have to be designed, developed, and tested in the field.

Unfortunately, a real war against cancer has never been mounted by thefederal government. To date, available federal funds have supported only asmall, intense skirmish by a limited number of investigators. The number ofinvading cancer cells and their effectiveness are difficult for one to realize.Each year, these marauding cells kill almost ten times as many U.S. citizens,more than 550,000, as were killed in the entire Vietnam conflict (58,150) thatcovered a period of nine years (1964—1973).From 1970 to 1995, roughly thesame period as the National Cancer Act, our national defense budget increased208%androsefrom$81.7billionto$252.2billion.Inpart,thisdefensebudgetis considered necessary by policymakers to prevent us from dying from war,yet it is over 100 times the amount of the budget of the National CancerInstitute (NC!), which supports research to protect U.S. citizens and othersaround the world from a far more probable and menacing killer.

Stealth cancer cells will attack and ultimately kill 1 out of every 4 Americans who are alive today. The two fields of dots in the cover design connotethe nearly 1,550 deaths from cancer per day in the U.S. This death rate issteadily increasing every year. However, during the past 10 years, U.S.Government funding for cancer research, when adjusted for inflation, hasincreased only 1%. Total federal research funding per year for the two leadingcancers diagnosed in the U.S. male (prostate and lung) would not representenough money to purchase three new fighter planes. Obviously, this does notreflect a Congressional commitment to a “waragainst cancer.―

Somehow in politics, taxes,and budgets, the Nation seemsto have lost a clearperspectiveon the important priorities. Maybe the advice of the newscommentatorSam Donaldson was correct when he suggested to us at a recent summit inWashington on the cancer problem—―Never try to get Congress to see the light;rather, make them feel the heat.―To thoseof us who are busy with the battle, thisseemsto be a very sadcommentary. Already we are called away from the field towrite extensive grant applications proposing our ideas, with less than a I in Schance of their being armed by funding. Our time is already limited, so how canwe now find even more time to educateour own legislators and fellow voters aboutthe value of cancer research?Equally alarming is a 1994 report by the NationalResearch Council that the number of grant applications from young scientistsunder the ageof37 declined 54% between 1985and 1993.We are losing over halfof our new young warriors just when new weaknessesare being revealed in ourenemy—thecancercell. Why arewe running training camps if the traineeswill notbe permitted to join the campaign? Furthermore, where will our replacementscome from in the future? Everyone has to wake up and shakeour leaders.

Congress and the public often ask us, ‘Whenare you going to cure cancer?―Thank goodnesswe have already cured some types of cancers, especially thosethat strike our young people. From 1973to 1990, the death rate from cancer from