title: Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.
abstract: 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.
authors.affiliation: National Cancer Institute, Bethesda, Maryland 20852, USA. kelloffg@mail.nih.gov
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Sigman
authors.forename: Homer L
authors.initials: HL
authors.lastname: Pearce
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.forename: V Craig
authors.initials: VC
authors.lastname: Jordan
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Vali A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
authors.forename: Jeri
authors.initials: J
authors.lastname: Kim
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Thomas
authors.forename: Helen E
authors.initials: HE
authors.lastname: Rhodes
authors.forename: Molly A
authors.initials: MA
authors.lastname: Brewer
authors.forename: Michele
authors.initials: M
authors.lastname: Follen
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Howard L
authors.initials: HL
authors.lastname: Parnes
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Alison A
authors.initials: AA
authors.lastname: Evans
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Blount
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Maley
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wang
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Paul F
authors.initials: PF
authors.lastname: Engstrom
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Hawk
authors.forename: Bernard
authors.initials: B
authors.lastname: Levin
authors.forename: William G
authors.initials: WG
authors.lastname: Nelson
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor