Abstract
Chemoprevention research in animals and humans has revealed that pathways in the cancer process are amenable to inhibition, reversal or retardation at various stages. We must therefore identify the key pathways in the evolution of cancer that can be blocked to prevent this carcinogenesis process. Current mechanistic approaches include administering agents which block the activation of carcinogens, promote the detoxification of carcinogens (Phase II enzyme inducers), enhance glutathione, block the production of reactive oxygen species, antioxidants, inhibit carcinogen uptake, promote repair processes, and block cell cycle progression. Some of the more promising strategies to prevent breast cancer include selective estrogen receptor antagonists and aromatase inhibitors, while for colon, skin and urinary bladder NSAIDs and polyamine synthesis inhibitors are highly preventive. Many of these strategies have been validated in human cancer prevention studies. Retinoids are differentiation and apoptosis inducers primarily, but act as agonists to the RAR and RXR receptors with many downstream effects. Newer safer rexinoids can prevent both ER positive and ER negative breast cancers. Targeted mechanistic approaches are currently being investigated, such as inhibition of lipoxygenase, PI3K/AKT/mTOR pathway inhibitors, EGF receptor tyrosine kinase inhibitors, histone acetylation/deacetylation and methylation/demethylation inhibitors. Most recently immunoprevention approaches have shown exciting promise and are being developed into the clinic. Future strategies include possible miRNA or antisense miRNA administration to prevent cancers. To conquer this diverse disease, multiple key pathways must be attacked at once for a predetermined period of time. It is becoming clear that each organ-specific cancer type may require a custom combination of prevention strategies to be successful.
Citation Format: Vernon E. Steele. New strategies for cancer chemoprevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN08-02.
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