| ABSTRACT: |
|
Chemoprevention is a strategy used to block the development of cancers
in human beings. This emerging field has broad potential for influencing
cancer incidence rates in defined high-risk groups and the general
population. In this review, we define some of the mechanisms of
carcinogenesis, describe some of the genetic markers of carcinogenesis,
and list possible biomarkers that may serve as surrogate end points in
chemoprevention studies. A major component of this review is a description
of the agents that are currently under investigation in animal systems or
in human trials. They are grouped according to the agents that block or
suppress mutation, such as oltipraz, selenium, vitamin C and the flavones,
or according to agents that block promotion and proliferation, such as
difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs,
and the vitamin A derivatives. We describe the issues that are considered
in the design of chemoprevention trials and in the phase I, II, and III
components of these trials. The following national trials are discussed:
the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate
Cancer Prevention Trial, which uses finasteride; and a Lung Cancer
Prevention Trial, which uses 13-cis-retinoic acid. The review ends with
some insights about future studies in chemoprevention. |