Tailoring cancer chemoprevention regimens to the individual

Abstract

The present article, which is a tribute to the memory of Dr. Edward Bresnick, emphasizes the importance of environmental and life-style factors for cancer causation in the human population and points out approaches to cancer prevention. These approaches include vaccinations for the prevention of cancers that are caused by infectious agents as well as the use of cancer chemopreventive agents. The use of tamoxifen and letrozole to prevent breast cancer, finasteride to prevent prostate cancer, sunscreens or topical applications of 5-fluorouracil to prevent sunlight-induced skin cancer, and aspirin or calcium to prevent colon cancer are a few examples of cancer chemoprevention in high risk individuals and in the general population. An underdeveloped area of cancer chemoprevention is the use of combinations of agents that work by different mechanisms. It was pointed out that animal studies indicate that many cancer chemopreventive agents inhibit carcinogenesis under one set of experimental conditions but enhance carcinogenesis under another set of experimental conditions. These observations suggest that tailoring the chemopreventive regimen to the individual or to groups of individuals living under different environmental conditions or with different mechanisms of carcinogenesis may be an important aspect of cancer chemoprevention in human populations. How to tailor cancer chemoprevention regimens to the individual is an important challenge for the future.

Silibinin Protects against Photocarcinogenesis via Modulation of Cell Cycle Regulators, Mitogen-Activated Protein Kinases, and Akt Signaling

“…PCNA, a subunit of DNA polymerase, plays a crucial role in DNA replication and repair and serves as a biomarker of proliferation (22). Earlier studies have reported that inhibition of DNA synthesis and cell proliferation by black tea, green tea, caffeine, or epigallocatechin is associated with their cancer chemopreventive efficacy (7,23). Silibinin also inhibited UVB-induced DNA synthesis and cell proliferation, as observed by a decrease in BrdUrd incorporation and PCNA-positive cells in uninvolved skin and tumors, suggesting a plausible role of in vivo antiproliferative effect of silibinin in its overall efficacy against UVB-induced tumorigenesis.…”

“…Several studies have shown that various phytochemicals protect against UVB-induced skin damages and cancer (5)(6)(7). Silymarin (flavonoid from milk thistle) and silibinin (bioactive component in silymarin) also cause strong prevention against UVB skin damages and photocarcinogenesis (8,9).…”

β-Escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21waf1/cip1 in colon cancer cells

“…Risk reduction by nutritional intervention holds promise for both prevention and control of colon cancer (2,3); an alternative approach to identify specific chemopreventive agents holds additional promise (4). Evaluation of food-based, naturally occurring phytochemicals and synthetic agents that can reduce the risk and retard or inhibit the development of colon cancer could lead to new strategies for colon cancer chemoprevention.…”

Carcinogenesis, cancer therapy and chemoprevention

“…[26][27][28][29] To complicate matters further, chemopreventive agents may promote cancer in some conditions. 30 In certain mice, sulindac, a nonsteroidal anti-inflammatory drug, prevents tumors in the small intestine but increases the incidence of tumors in the large intestine. 31 Retinoic acid prevents papillomas but accelerates progression from papillomas to carcinomas.…”