Progress in clinical chemoprevention.
Chemoprevention has four goals: (1) inhibition of carcinogens, (2) logical intervention for persons at genetic risk for cancer, (3) treatment of precancerous lesions, and (4) confirmation and translation of leads from dietary epidemiology into intervention strategies. The National Cancer Institute has described a multidisciplinary, cancer science-based program for chemopreventive drug development that addresses these objectives, and has collaborated with the US Food and Drug Administration to provide consensus guidance for applying this approach. A critical component is the identification and characterization of intermediate biomarkers of cancer and their validation as surrogate end points for cancer incidence in clinical chemoprevention trials. More than 40 agents in the program are currently on the clinical development path (preclinical toxicology and phase I clinical safety studies or phase II/III efficacy trials), with the major effort in phase II studies to identify and characterize intermediate biomarkers. The continually advancing knowledge of molecular and tissue-based carcinogenesis mechanisms will provide leads to new chemopreventive agents with increased specificity for carcinogenesis-related activities and, hence, reduced toxicity by virtue of minimal effects on normal cell and tissue functions. Results from the Human Genome Project will help identify and evaluate the potential for chemopreventive intervention in cohorts at genetic risk and will provide specific target lesions for intervention strategies.
Kelloff
G J
GJ
Division of Cancer Prevention and Control, Chemoprevention Branch, National Cancer Institute, Bethesda, MD 20852, USA.
Hawk
E T
ET
Karp
J E
JE
Crowell
J A
JA
Boone
C W
CW
Steele
V E
VE
Lubet
R A
RA
Sigman
C C
CC
D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D005069:Evaluation Studies as Topic; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D010601:Pharmacology, Clinical
D016588:Anticarcinogenic Agents; D015507:Drugs, Investigational