Pharmacology of Chemoprevention

Carcinogenesis is a chronic and multistep process that results in malignancy. Malignant cells acquire the ability to invade or metastasize. Metastasis is often the first evidence of malignant disease. During the continuum of carcinogenesis, therapeutic interventions can be used to arrest or reverse this process. This is known as cancer chemoprevention. Effective cancer chemoprevention should suppress or block the clinical manifestation of malignancies by treating lesions before clinical signs or symptoms arise.

Chemoprevention Trials

Cancer prevention efforts have been a long and arduous process. As the biological basis for carcinogenesis continues to be elucidated, different strategies for prevention have emerged. The success of recent clinical trials designed to prevent cancer in patients who are at increased risk of cancer (cancer "chemoprevention" trials) suggests that chemoprevention is a rational and appealing treatment strategy. Success in the prevention of epithelial cancers suggests that chemopreventive agents can interrupt the carcinogenic process.

Cancer Risk Reduction

Cancer Risk Reduction (Diet/Smoking Cessation/ Lifestyle Changes)
Many cases of cancer can be prevented. Generally, people can reduce their risks for developing cancer by making wise lifestyle choices such as eating low-fat, high-fiber diets that include a variety of vegetables and fruits, avoiding tobacco use, being physically active, and minimizing sun exposure. Specific genetic susceptibilities, however, can influence cancer risk associated with certain lifestyle factors, and variation in risk exists among individuals. Guidelines for implementing lifestyle choices to reduce cancer risk have been formulated to help people adopt cancer-protective behaviors.

Antioxidants: Carcinogenic and Chemopreventive Properties

Chemical carcinogens, which are present widely in our environment, are considered to play an important role in the causation of most human cancers. They may be classified into genotoxic and nongenotoxic types, the former including nitrosamines, aromatic hydrocarbons, aromatic amines, and nitrofurans, and the latter being exemplified by peroxisome proliferators, antioxidants, chlorinated pesticides, uracil, and D-limonene. For primary prevention of human cancer, it is essential that we eliminate carcinogens as far as possible and ingest possible chemopreventors.

Animal Models for Colon Cancer Chemoprevention

Colorectal cancer is a tumor of colon and rectum, which occurs with high frequency in both men and women in Western countries. Most cases of colorectal cancers arise in a benign adenoma; some evidence suggests that some cancers arise directly from the mucosal cells. With regard to genetic mechanisms of colorectal cancer, the disease appears to result from an increase in the number of genetic mutations, mostly acquired, that accumulate in the genome of the evolving cancer cell.

Tobacco Carcinogenesis

Tobacco carcinogenesis is the process by which tobacco products and their constituents interact with cells to cause cancer. Cigarettes are the main tobacco product worldwide. Manufactured cigarettes are available in all countries, but in some areas of the world, roll-your-own cigarettes are still popular. Other smoked products include kreteks, clove-flavored cigarettes popular in Indonesia, and "sticks" which are smoked in Papua, New Guinea.

Multistage Carcinogenesis

Ahallmark of carcinogenesis, the process of tumor development in an organism, is a long latent period with no clinical evidence of disease. The agedependent incidence of diagnosed cancers in humans suggests that carcinogenesis commonly proceeds via four to seven independent rate-limiting steps. Both animal carcinogenesis models and the analysis of human clinical samples support this stepwise progression of tumorigenesis.

Hormonal Carcinogenesis

The endocrine system and its numerous hormones function to integrate genetically encoded developmental programs and environmental signals and regulate the myriad biochemical processes, such as cell proliferation, differentiation, and death, required to maintain homeostasis within boundaries compatible with life. It is becoming increasingly clear that aberrations in the control of these hormone-regulated processes contribute to the genesis of many forms of cancer. In specific instances, hormones also appear to act through nonreceptor-mediated mechanisms to contribute to carcinogenesis.

Carcinogenesis: Role of Reactive Oxygen and Nitrogen Species

Carcinogenesis is a complex multistage process often taking decades until malignancy appears. Conventionally, the carcinogenic process has been divided into three main stages: initiation, promotion, and progression. Initiation requires an irreversible genetic damage causing mutations in transcribed genes. Promotion consists of a potentially reversible oxidant-mediated conversion step followed by a clonal expansion of the initiated cells into benign tumors, which can progress to malignancy when they acquire many additional genetic changes.