Abstract
Cancers derive from step by step processes which are differentiated by the progressively accumulated mutations. For some tumors there is a clear progressive advancement from benign lesions to malignancy and for these, preventive screening programs exist. In such cases having those benign lesions are a clear indicator of predisposition while for some other cases, familial patterns of cancer incidence and the identification of mutations are the main indicators of higher risk for having the disease. For patients identified as having predisposition, chemoprevention is a goal and in some cases a possibility. Chemoprevention is the use of any compound, either natural or synthetic that abrogates carcinogenesis or tumor progression, through different mechanisms, some of which have already been described. For example, the classic mechanisms may involve activation of free radical scavenging enzymes, control of chronic inflammation, and downregulation of specific signaling pathways. More recently, epigenetics allowed further understanding of the chemopreventive potential of several agents, such as sulforaphane, green tea derived compounds, resveratrol, isoflavones, and others which we exploit in this review article. Throughout the text we discuss the properties compounds should have in order to be classified as chemopreventive ones and the challenges in translational research in this area, as lots of the success achieved in vitro cannot be translated into the clinical settings, due to several different drawbacks, which include toxicity, cost, dose definition, patient adherence, and regimen of use.
Highlights
Fabiana Henriques Machado de Melo, Julia Salles Oliveira, Viviani Olivastro Bressani Sartorelli and Wagner Ricardo Montor*
This result is in agreement with extensive data from the literature that shows that women from Asia, where there is a higher intake of soy-based foods, have lower incidence of breast cancer, suggesting the participation of IF in epigenetic reprogramming of breast epithelial cells
As we understand carcinogenesis and tumor progression more and more we identify individuals who are at increased risk of developing cancer
Summary
In order to understand the possibilities available to interrupt carcinogenesis and tumor progression, either through chemotherapy or chemoprevention, it is of vital importance to have a general view of the several steps necessary for tumor formation. Given that a high proportion of breast cancers express estrogen receptors and depend on it for proliferation, the use of estrogen receptor antagonists has an important role in chemoprevention [20] All of those present anti-tumoral effects when used over tumor cell cultures and revert the apparent tumoral phenotype at some level, but with the exception of NSAIDs preventing intestinal cancer recurrence or occurrence in high risk populations, the clear observation that the consumption of fruits and vegetables prevents several kinds of cancer, and that prevention of breast cancer recurrence benefits from the use of synthetic selective estrogen receptor modulators such as tamoxifen and raloxifen, no single molecule has been reported to be effective in humans and that might be because they exert their effects in specific tumors only and in higher concentrations or in combination with other molecules, or still their distribution through the body might hinder direct action on specific cells, which is not the case for tissue cultures in the lab [11]. It might be that the molecules tested are not the ones responsible for prevention or it only acts when in combination with others, which might be the case as we have different tumorigenesis mechanisms that might need to be hindered by multiple chemopreventive agents at the same time [25,26,27]
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