Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.
This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.
Kelloff
Gary J
GJ
National Cancer Institute, Bethesda, Maryland 20852, USA. kelloffg@mail.nih.gov
Lippman
Scott M
SM
Dannenberg
Andrew J
AJ
Sigman
Caroline C
CC
Pearce
Homer L
HL
Reid
Brian J
BJ
Szabo
Eva
E
Jordan
V Craig
VC
Spitz
Margaret R
MR
Mills
Gordon B
GB
Papadimitrakopoulou
Vali A
VA
Lotan
Reuben
R
Aggarwal
Bharat B
BB
Bresalier
Robert S
RS
Kim
Jeri
J
Arun
Banu
B
Lu
Karen H
KH
Thomas
Melanie E
ME
Rhodes
Helen E
HE
Brewer
Molly A
MA
Follen
Michele
M
Shin
Dong M
DM
Parnes
Howard L
HL
Siegfried
Jill M
JM
Evans
Alison A
AA
Blot
William J
WJ
Chow
Wong-Ho
WH
Blount
Patricia L
PL
Maley
Carlo C
CC
Wang
Kenneth K
KK
Lam
Stephen
S
Lee
J Jack
JJ
Dubinett
Steven M
SM
Engstrom
Paul F
PF
Meyskens
Frank L
FL
O'Shaughnessy
Joyce
J
Hawk
Ernest T
ET
Levin
Bernard
B
Nelson
William G
WG
Hong
Waun Ki
WK
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000517:prevention & control; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D006801:Humans; D007239:Infections; D007249:Inflammation; D008297:Male; D008991:Monitoring, Physiologic; D009375:Neoplasms, Glandular and Epithelial / Q000517:prevention & control*; D015398:Signal Transduction
D014408:Biomarkers, Tumor