[CANCER RESEARCH 63, 5649–5655, September 15, 2003]
Review and Meeting Report
Frontiers in Cancer Prevention Research1
Anita L. Sabichi, Marie-France Demierre, Ernest T. Hawk, Caryn E. Lerman, and Scott M. Lippman2
Departments of Clinical Cancer Prevention and Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
[A. L. S., S. M. L.]; Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118 [M-F. D.]; Gastrointestinal and Other Cancer Research
Group, National Cancer Institute, NIH, Division of Cancer Prevention, Bethesda, Maryland 20892 [E. T. H.]; and Abramson Cancer Center at the University of Pennsylvania,
Philadelphia, Pennsylvania 19104 [C. L.]
In October 2002, the AACR pioneered and hosted the first major
annual meeting devoted to cancer prevention. This signal event
marked the rapid movement of cancer prevention to the forefront of
feasible modalities for reducing the burden of cancer. Within only the
past five years, the Food and Drug Administration issued its first two
expressly chemoprevention-related approvals, one of tamoxifen for
reducing breast cancer risk (1), the other of celecoxib (2) in the setting
of FAP.3Abundant other signs also reflect a sea change in cancer
prevention. Recently reported studies demonstrated the ability of
finasteride to reduce prostate cancer development and of NSAIDs to
reduce the burden of sporadic adenomas (3–5). Molecular cancer risk
assessment and cancer-risk-reduction surgery have become standard
approaches (6, 7). Traditionally treatment-oriented institutions (cancer
centers and National Cooperative Oncology Groups) are leading sem-
inal cancer prevention trials (1–3, 5). There has been a paradigm shift
in oncology from cancer treatment toward cancer prevention, mirror-
ing a similar decades-old shift in cardiology. To reduce the risk of
myocardial infarctions, it was necessary initially to identify the prom-
inent risk factors and test preventive interventions. This process led to
a better understanding of, educating the public and health-care prac-
titioners about, and developing interventions that effectively modulate
many cardiovascular risk factors (e.g., hypertension, hyperlipidemia),
which have come to be considered bona fide diseases. This transition
from “risk factor” to “disease” reveals a subtle evolution in our
definitions of health and disease. Whereas traditional disease concepts
focused narrowly on obvious symptomatology, newer concepts rec-
ognize that most illnesses, including cancer, have long, clinically
silent ramping-up phases of evolving molecular and cellular aberra-
tions. Therefore, the science and medicine of cancer prevention chal-
lenge our traditional definition of disease, demanding a subtler view
composed of formerly defined risk factors that can be treated preven-
tively over sustained periods.
The AACR prevention meeting brought together academic, gov-
ernment, industry and advocacy-group leaders to focus on a compre-
hensive agenda of prevention disciplines, such as chemoprevention,
risk-reduction surgery, behavioral science and health services re-
search, diet and nutrition, molecular genetics, epidemiology, and
imaging. Extraordinary advances in the molecular biology of cancer
susceptibility and carcinogenesis have raised important opportunities
(even the responsibility) to apply this biology to the multidisciplinary
development of novel clinical cancer prevention approaches. A wave
of new technology (e.g., high-resolution endoscopy, laser-capture
microdissection, multiplex gene/expression/protein arrays and small
interfering RNA) is rapidly increasing our understanding of neoplastic
evolution. We now understand that this process involves mutations in
key tumor suppressor genes and/or oncogenes, epigenetic changes via
aberrations of histone acetylation or DNA methylation, genetic insta-
bility, and defects in signal transduction (7–9), with clonal expansion
(10) and, remarkably, intraepithelial spread/metastasis of premalig-
nant cells (11). Through cross-sectional and prospective validation,
these molecular alterations can be used as (a) markers of cancer risk
and susceptibility to carcinogenesis, (b) targets for developing novel
preventive interventions, and (c) intermediate measures of response
that can help in identifying and developing new cancer chemopreven-
tive agents (12). This article reviews important areas and future
directions of the new science emerging in the field of cancer preven-
tion and presented during the first AACR Cancer Prevention conference.
Genetics and Molecular Epidemiology
Studies of genetics and molecular epidemiology are increasing our
understanding of inherited susceptibility to carcinogenic exposures
and interindividual variability in this susceptibility. The study of
gene-gene and gene-environment (diet, diet-related factors, growth
factors, hormones) interactions is a major component of this work.
Genetic variants regulating steroid hormone metabolism (e.g.,
SRD5A2, CYP17) may partly explain ethnic differences and interin-
dividual variability in hormone-related cancer risk (13, 14). The
development of tobacco-related cancer only in subsets of smokers
now can be explained, in part, by genetically mediated differences in
tobacco carcinogen activation (15). Genetic polymorphisms that in-
teract with dietary exposures to increase cancer susceptibility have
been identified (16). This new knowledge will facilitate the design of
novel prevention approaches for targeting tailored interventions on
Preventive pharmacogenomics is a new field that increases our
understanding of interindividual variability in agent response attrib-
utable to inherited variations in drug metabolism and molecular drug
targets (17–20). The preventive activity of isotretinoin in head and
neck carcinogenesis may depend on cyclin D1 genotype (18), aspirin
activity in colorectal neoplasia may depend on specific polymor-
phisms of CYP 2C9 (19), finasteride activity in prostate cancer may
depend on polymorphisms of SRD5A2 (3, 13) and tamoxifen may
Received 7/23/03; accepted 8/11/03.
The costs of publication of this article were defrayed in part by the payment of page
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18 U.S.C. Section 1734 solely to indicate this fact.
1This work was supported in part by Cancer Center Support Grant CA16672 from the
National Cancer Institute, NIH. This article reports on the AACR conference “Frontiers in
Cancer Prevention Research: Genetics, Risk Modeling, Molecular Targets for Chemopre-
vention, Behavioral Prevention Research, Clinical Prevention Trials, Science and Public
Policy,” held in Boston, MA, October 2002, chaired by Waun Ki Hong, M.D., and
co-chaired by Raymond N. DuBois, Ph.D., M.D., Brian E. Henderson, M.D., Caryn E.
Lerman, Ph.D., and Scott M. Lippman, M.D.
2To whom requests for reprints should be addressed, at the Department of Clinical
Cancer Prevention, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe
Boulevard, Unit 236, Houston, TX 77030-4009. E-mail: email@example.com.
3The abbreviations used are: FAP, familial adenomatous polyposis; COX-2, cyclooxy-
genase-2; EGFR, epidermal growth factor receptor; LOX, lipoxygenase; PPAR, peroxi-
some proliferator-activated receptor; NSAID, nonsteroidal anti-inflammatory drug; IEN,
intraepithelial neoplasia; SERM, selective estrogen receptor modulator; IGF-1, insulin-
like growth factor; SELECT, Selenium and Vitamin E Cancer Prevention Trial; HPV,
human papillomavirus; NCI, National Cancer Institute; PCPT, Prostate Cancer Prevention
Trial; ER, estrogen receptor.
reduce breast cancer risk in BRCA-2 but not BRCA-1 mutation carriers
(20). Tamoxifen is metabolized by SULT1A1, CYP2D6, or CYP3A4,
which may affect its bioavailability or the generation of metabolites
associated with adverse events. Chemopreventive studies may not
detect positive effects of preventive agents that work only in a
study-population subset characterized by a specific genotype. Another
example of a pharmacogenomic approach to cancer prevention is the
potential tailoring of smoking-cessation pharmacotherapies based on
smokers’ genotypes (21).
Research in genetics and molecular epidemiology also is linked
tightly with surgical risk reduction approaches. Prophylactic resection
of high-risk tissue in certain germ-line mutation carriers, including
prophylactic thyroidectomy in patients with MEN2a, MEN2b, famil-
ial medullary thyroid carcinoma, or Ret mutations, bilateral mastec-
tomy and oophorectomy to reduce breast cancer risk, and ovarian
cancer risk in carriers of BRCA1 and BRCA2 mutations, and colec-
tomy in patients with FAP and hereditary nonpolyposis colorectal
cancer (HNPCC; Refs. 22–24), have become a standard albeit radical
form of prevention or risk reduction. Novel statistical approaches are
being developed for modeling cancer risk and the potential efficacy of
surgical risk reduction (25). As is discussed in more detail in the
Behavioral Science Research Section, behavioral-science and health-
services studies complement genetic and molecular epidemiology in
developing clinical approaches for reducing cancer risk in susceptible
populations. Assessing surrogate/target-tissue biomarker correlations
in carcinogenesis are important new areas of molecular epidemiology
A primary area of biomarker research is the prevention of tobacco-
related cancers (27). Metabolically activated forms of these carcino-
gens form DNA adducts that can cause permanent critical gene
mutations leading to the loss of normal growth control mechanisms.
Chronic exposure to tobacco results in a constant barrage by over 60
carcinogens on DNA, promoting multiple genetic changes leading to
cancer. Specific biomarkers and methods are now available for quan-
titating the cellular uptake of a variety of tobacco carcinogens and the
associated formation of DNA-binding fragments and adducts (28).
The early detection of cancer and identification of high-risk IEN are
major priorities for cancer research. This work includes the identifi-
cation of molecular aberrancies in exfoliated cells and the use of novel
imaging technologies (29). A variety of assays might facilitate the
identification of genetic and epigenetic alterations. These approaches
could include the use of microsatellite, mitochondrial DNA, and
promoter-methylation analyses of easily collected specimens (e.g., in
saliva and urine; Ref. 30). Proteomic analyses may play an important
role in early cancer detection and chemoprevention in high-risk
groups (31). Lessons learned from recent studies of prostate-specific
antigen (PSA) for early detection of prostate cancer underscore the
importance of carefully planned biomarker discovery, development,
and validation studies such as those in the NCI Early Detection
Research Network (12). The AACR formed the Task Force on the
Treatment and Prevention of IEN to address the crucial issue of IEN
end points for chemoprevention trials (32). A new prevention task
force has been formed to build on the IEN Task Force and focus on
molecular markers of cancer risk, early detection, and preventive
(surrogate-end-point biomarkers) activity (7, 33, 34).
Molecular Targeting in Chemoprevention
In the past, chemotherapy involved mainly toxic i.v. drugs, and
chemoprevention mainly vitamins and minerals (35). A revolution in
drug development has been sparked by molecular targeting research
that has led to the development of many promising new drugs (e.g.,
oral drugs that are low in toxicity) applicable to prevention and/or
therapy. There is intense interest in studying the chemopreventive
potential of molecular-targeted drugs such as EGFR inhibitors,
SERMs and aromatase inhibitors, which initially were used as cancer
therapy (36). Conversely, agents such as COX-2 inhibitors that have
been studied in cancer chemoprevention are now under active study
for cancer therapy. In many instances, molecular-targeting agents may
be developed both for cancer therapy and prevention within the same
Phase I/II trials assessing toxicity and optimal biological dose. Iden-
tifying multiple molecular targets for effective combinations of pre-
ventive agents is a major focus of chemoprevention study (37).
Developing targeted drugs for prevention involves a number of
complicated signaling pathways/targets [e.g., LOXs, protein kinase G
(PKG), PPARs, activator protein-1 (AP-1), nuclear factor-?B (NF-
?B), signal transducer and activator of transcriptions (STATs), p53,
MMPs, GSK3?, Akt] and approaches (e.g., receptor tyrosine kinase
inhibitors, demethylating agents, histone deacetylase inhibitors, anti-
sense molecules, and gene therapy) and determining the effects of
active agent classes, including complicated cross-target effects (e.g.,
“selective” COX-2-inhibiting NSAIDs) and cross-organ site (e.g.,
estrogens in prostate carcinogenesis effects; Refs. 36–45). For exam-
ple, the preventive activity of NSAIDs may be mediated via molecular
target mechanisms other than COX-2, such as PKG, 15-LOX, and
PPARs (44, 45), which, therefore, serve as new potential targets for
drug development. The loss of normal apoptotic mechanisms is a
hallmark of cancer development, and, therefore, targeting apoptosis-
inducing molecules is a high priority of preventive agent development
(46). Gene-based animal model development (e.g., tissue-specific,
temporally regulated transgenic, dominant-negative, and knockout
models) will be a valuable tool for decoding the complicated tissue-
specific mechanisms of action of different preventive agents (47).
Preclinical studies of UVB- and UVA-signaling pathways have iden-
tified several potential new targets, including AP-1, COX-2, p38
mitogen-activated protein (MAP) kinase, and phosphatidylinositol
3?-kinase (PI3K), for skin cancer prevention (48, 49).
Potential preventive agents such as natural products and their
derivatives and synthetic analogues are being identified from terres-
trial (e.g., EGFR inhibitors, protease inhibitors, new triterpenoids,
dietary polyphenols, green tea, resveratrol, and curcumin) and marine
plants, and soil organisms (38, 49–51). A recent study found that the
natural plant product deguelin has potent apoptotic effects in prema-
lignant lung cells through the suppression of the phosphatidylinositol
3?-kinase (PI3K)/Akt pathway (52).
The study of retinoids in head and neck carcinogenesis provides a
molecular model of the principle that chemoprevention agents can
delay the onset of clinically detected cancer. Mechanisms of cancer
delay may involve suppression of genetic instability (53) and detour-
ing multistep carcinogenesis down alternate molecular pathways (54).
A recent translational study suggests that retinoic acid produces head
and neck cancer delay via a molecular detour at 11q13 (cyclin D1;
Findings from clinical cancer chemoprevention trials have contrib-
uted to the maturation of cancer prevention in general. Early trials of
retinoids in preventing skin and head and neck cancers provided the
proof of principle for chemopreventive approaches (35, 36, 55–58).
“Standard” regimens in the arsenal of chemoprevention that have been
in use for some time include hepatitis B vaccine to prevent liver
cancer (59), Bacillus Calmette-Gue ´rin (BCG) and valrubicin to treat
bladder IEN, topical 5-fluorouracil, diclofenate, masoprocol, and ami-
REVIEW AND MEETING REPORT
nolaevulinic acid (with photodynamic therapy) for treating skin IEN
(32, 54). These prevention gains were consolidated by more recent
results from several prospective chemoprevention studies such as
tamoxifen for breast cancer prevention [National Surgical Adjuvant
Breast and Bowel Project (NSABP) P1 (Breast Cancer Prevention
Trial) and B24 and The International Breast Cancer Intervention
Study (IBIS); Refs. 60–62], sulindac or celecoxib for reduction of
colonic polyp burden in FAP, aspirin or calcium for reducing sporadic
adenoma risk (2, 4, 5, 63–65), and finasteride for reducing prostate
cancer risk (3).
As illustrated by hepatitis B vaccine to prevent liver cancer (59),
vaccines are an important area of development with high clinical
potential for cancer prevention. For example, persistent HPV infection
in the cervix is linked to the development of cervical intraepithelial
neoplasia and cancer, and virtually all cervical cancers are HPV DNA
positive. Therefore, developing vaccines against HPV would repre-
sent a unique chemoprevention approach (66) because data suggest
that the majority of vaccinated women develop high HPV antibody
titers. Defining specific antigens and immunization protocols that
could effectively prime the immune system to eliminate cancer before
its clinical manifestation is an intriguing approach. A major focus of
vaccine development for cancer prevention is targeting antigens dif-
ferentially expressed by cancer or IEN cells but not by normal cells.
For example, the antigens MUC1 (expressed in polyps but not in
normal colon cells) and cyclin B1 (aberrantly expressed by tumor
cells; Refs. 67 and 68) might be important targets for development of
an effective vaccination against colon IEN and cancer.
Although Food and Drug Administration-approved in three breast-
cancer prevention settings, tamoxifen illustrates the imposing chal-
lenge in disease prevention of balancing complex agent risks and
benefits. Tamoxifen risks include endometrial cancer and pulmonary
embolism. Strategies for improving the risk-benefit ratio of tamoxifen
(e.g., by lowering the dose) are under investigation (69). Models
estimating an individual’s breast cancer risk and potential benefits and
the risks of intervention with tamoxifen are a challenge to incorporate
into clinical practice (61). Current evidence suggests that tamoxifen,
other SERMs, and other hormone-directed agents do not prevent
ER-negative breast cancers. Several agents, e.g., RXR-selective reti-
noids, COX-2 inhibitors, EGFR inhibitors, can suppress the develop-
ment of ER-negative breast cancer in animals (61, 70), and a combi-
nation of these and ER targeting agents may prove to be the most
effective strategy to prevent breast cancer in the widest possible
population of women at risk.
In lung cancer chemoprevention, clinical and preclinical mechanis-
tic studies found a harmful interaction of ?-carotene with cigarette
smoke (36). Recent study has focused on high-risk former smokers
(71) and has produced some promising early results (27, 72). Study of
the metabolism of tobacco carcinogens has led to chemoprevention
trials with carcinogen-DNA adduct end points. Consistent with the
prevention-therapy overlap discussed above, recent lung-cancer pre-
vention approaches include the use of farnesyl transferase inhibitors
or EGFR tyrosine kinase inhibitors to reverse IEN in patients with a
history of smoking-related cancers. New methods of agent delivery,
such as aerosolized inhalation, may improve the therapeutic index of
preventive agents in accessible organs such as the lung (73).
Prophylactic colectomy is the standard treatment for patients with
FAP, chronic ulcerative colitis (CUC), and, to a lesser extent,
HNPCC. The timing of surgical resection depends on the presence of
high-grade dysplasia in CUC, and the extent of adenoma burden in
FAP, but the extent of resection in FAP is controversial. Morbidity of
colectomy is high, and focus on alternative preventive interventions
has led to randomized controlled trials of the nonspecific COX inhib-
itor, sulindac, and the COX-2 inhibitor, celecoxib, which were shown
to reduce colonic polyp burden in patients with FAP (2, 63). Oxidative
metabolism of the omega 6 polyunsaturated fatty acid (PUFA) arachi-
donic acid by COX-2, and 5- and 12-LOX-mediated pathways has
been linked to tumorigenesis in animal models and in humans. PUFA
metabolism exists in a dynamic balance that shifts during carcinogen-
esis to 5- and 12-LOX and COX-2 pathways and away from 15-
LOX-1 or -2 pathways, the products of which appear to be anticarci-
nogenic (45, 74, 75).
Prostate cancer prevention is a major focus of clinical chemopre-
vention (41, 76, 77). Presented while still ongoing during the AACR
Frontiers conference, the landmark Southwest Oncology Group
(SWOG)-led NCI Intergroup PCPT was stopped early and reported in
July 2003 (3). The PCPT tested the 5-?-reductase-targeting agent
finasteride versus placebo for 7 years in 18,882 men, ages ?55 years.
Finasteride produced a 24.8% reduction (P ? 0.001) in the period
prevalence of prostate cancer. More men developed high-grade tu-
mors (Gleason scores ?7) in the finasteride arm (6.4%) than in the
placebo arm (5.1%; P ? 0.005). Urinary symptoms/events related to
benign prostatic hypertrophy were more common in men on placebo,
whereas sexual side effects were more common in men on finasteride.
Therefore, men considering finasteride for prostate cancer prevention
must carefully evaluate the possible benefits of prostate cancer risk
reduction and reduced urinary problems against increased sexual side
effects and potential risks of high-grade disease. The SELECT is an
ongoing trial testing selenium and vitamin E in a 2 ? 2 factorial
design based largely on provocative secondary analyses of the two
agents in prior NCI Phase III prevention trials (selenium tested in skin
cancer prevention; vitamin E in lung cancer prevention) (36). The
accrual goal is 32,400 men at risk for developing prostate cancer
because of age (African Americans, ?50 years; other men ?55
years). Activated in July 2001, study accrual is 75% complete in only
2 years. Both the SELECT and PCPT have invaluable biorepositories
(e.g., serum, WBCs, and malignant and nonmalignant prostate tissue)
for translational molecular studies of prostate carcinogenesis, cancer
risk, and intervention effects (78).
Nutritional and Energy Balance
Epidemiological studies have identified at-risk populations and
potential interventions associated with reduced cancer risk. The re-
sults of these studies are important for generating prevention hypoth-
eses (79) but should be confirmed in rigorous randomized controlled
trials before public health recommendations are made (80). Epidemi-
ology has linked diet and diet-related factors, e.g., obesity, to cancer
risk and prevention. Preclinical studies are shedding new light on the
relative contributions of dietary fat, obesity, caloric restriction, and
exercise to cancer risk (81, 82). In particular, recent studies have
shown that moderate caloric restriction delays mammary tumor de-
velopment and death in genetically predisposed mice. Data suggest
that endocrine mechanisms, such as IGFs/insulin resistance, may
mediate these effects. IGF-1 is a key regulator of the endocrine,
paracrine, and autocrine-signaling network that controls energy me-
tabolism and has been linked to risk of certain cancers, including
advanced/aggressive prostate cancer (83). Further understanding of
IGFs as a marker of cancer risk and prevention will be important.
Based on epidemiologic data (84), low-fat, high-fiber and fruit-and-
vegetable diets have been tested in recent randomized sporadic ade-
noma trials (85, 86), which, although negative, underscore the evolu-
tion of the epidemiology of diet and nutrition. Basic science
assessments of nutrition and energy balance and interactions in cancer
development or prevention will be critical to advances in the field.
REVIEW AND MEETING REPORT
Behavioral Science Research
Tobacco control remains our greatest challenge (87). In 2002,
tobacco was responsible for over 4 million deaths, and it is predicted
that in 2030, more than 10 million tobacco-related deaths will occur
worldwide, 7 million in developing countries. In the United States
alone, tobacco is responsible for more than 100 billion dollars in
annual economic costs. The future of cancer prevention also depends
heavily on study determinants of health-behavior changes and evalu-
ation of interventions to improve the outcomes of and participation in
cancer prevention programs.
Behavioral science and health services investigations are vital to
advance the science of cancer prevention and to identify the optimal
ways to apply these advances in practice to reduce cancer risk. One
important area of behavioral science seeks to elucidate the determi-
nants of cancer risk behaviors, including interacting biological, be-
havioral, and social factors. Emerging research in this area is identi-
fying genetic polymorphisms that increase the likelihood of smoking
initiation and addiction to nicotine (88–90) and that moderate the
efficacy of tobacco control interventions (91). The genetic underpin-
nings of other cancer risk behaviors, such as alcohol use (92) and
obesity (93) are also being elucidated. Advances in our understanding
of the behavioral, social, and cultural bases of tobacco use, eating
behavior, and physical activity will also greatly facilitate the devel-
opment of improved interventions for behavioral risk factor reduction
Behavioral science and health services research complement re-
search in genetic susceptibility to cancer. Our ability to identify
individuals who carry cancer susceptibility mutations brings respon-
sibility to obtain adequate informed consent and education (97–102).
One important contribution of behavioral science research has been to
provide empirical evidence that the majority of participants who
receive genetic testing for cancer susceptibility do not suffer signifi-
cant adverse psychological consequences (100); however, genetic
testing may generate specific stresses related to the testing process
(101, 102) or may lead to significant distress in subgroups of vulner-
able participants (103). Moreover, until cancer-predisposing alter-
ations can be corrected at the molecular level, there is a need to
enhance adherence to early cancer detection in persons identified as
mutation carriers (104–106). It is possible that communicating ge-
netic risk to individuals will motivate changes in cancer-related be-
haviors, such as tobacco use; however, much remains to be learned in
this area (107, 108). Of course, to realize the full potential of new
behavioral prevention and chemoprevention interventions, participa-
tion and long-term behavioral compliance are key (102, 109, 110).
The successful translation of cancer prevention research also re-
quires an adequate understanding of several issues addressed by
health services research. For example, research is elucidating factors
that influence decisions to participate in genetic testing, and decision-
making about detection and risk reduction strategies for which a firm
base of evidence has not yet accumulated (99, 111). New information
is also emerging regarding the economic and quality-of-life outcome
of genetic testing and cancer prevention approaches (112, 113). Re-
search has also identified potential barriers to the effective and ethical
translation of cancer prevention research, including a lack of provider
readiness (114). A proactive approach to addressing these barriers is
essential to promote the diffusion of science-based cancer prevention
Future Challenges and Directions
Cancer prevention must overcome substantial obstacles and chal-
lenges unique to this field. Low participation by minority and medi-
cally underserved populations (115) remains a major problem of
cancer prevention practice or research, and the NCI is vigorously
addressing this obstacle. Meeting the needs of special populations will
require novel, effective and insightful measures, such as are being
tested in the SELECT and other large NCI-supported chemopreven-
tion trials. Complex risk-benefit and drug-interaction profiles (1, 3,
61, 76, 116–118) need to be worked out so that the results of positive
cancer prevention trials can lead to standard prevention regimens for
the groups most likely to benefit. The identification of these groups
will require the development of molecular risk models and pharma-
cogenomic profiles. Innovative study designs and analysis methods
are needed for translational trials that incorporate complex multiple
biomarker end points (119). Important opportunities for cross-disci-
pline development are therapeutic trials in cancer settings with a
prevalence of early subclinical lesions. These trials should include
nested prevention endpoints (e.g., ACFs in colon cancer trials) when
the study agents have preventive potential based on their mechanistic
and safety profiles.
Disease prevention is a complex endeavor and outcomes models
integrating multiple cancer and other clinical end points are needed to
comprehensively assess promising cancer preventive agent classes,
such as SERMs, 5? reductase inhibitors (5ARIs), PPARs, and
NSAIDs, which can beneficially and adversely affect different dis-
eases, including cancers and cardiovascular, inflammatory, brain,
endocrine, and bone diseases. Future molecular studies of aging may
find that atherogenesis, carcinogenesis, and other older age-related
diseases share certain common molecular alterations that could be
targeted by the same prevention approaches (120–126). The need to
integrate prevention into the healthcare system is increasing, because
it is predicted that without major advances in cancer prevention and
treatment, growth and aging of the U.S. population will double the
cancer burden in the next 50 years (127). The apparent efficacy of
several agents (e.g., folic acid, NSAIDs, calcium, and statins) against
several common chronic diseases of aging (e.g., cardiovascular dis-
ease, carcinogenesis, and neurodegenerative diseases) support this
Many strong present foci and future visions of the science and
practice of cancer prevention were presented during the AACR Fron-
tiers meeting in Boston. These presentations highlighted the promis-
ing, innovative studies in chemoprevention, risk-reduction surgery,
behavioral science and health services research, diet and nutrition,
molecular genetics, epidemiology and imaging that have brought
about a sea change in, and hold the keys to the future of, cancer
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REVIEW AND MEETING REPORT
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