Chemoprevention - Strategies, Mechanisms, and Examples

Introduction:

Cancer continues to be a major global health concern, affecting millions of lives each year. Due to the consistent rise in global cancer cases and the associated negative impact on health and healthcare expenses, there is a growing interest in finding strategies for preventing the disease. One promising approach is chemoprevention, which involves using natural, synthetic, or biological substances to reverse, suppress, or prevent the early stages of cancer development or the progression of precancerous cells into invasive cancer. With advancements in the understanding of the biology of cancer and the identification of potential molecular targets to disrupt this process, interest in this field of research has significantly increased. The successful chemoprevention of breast, prostate, and colon cancer, as well as the existence of FDA (Food and Drug Administration) - approved agents for the treatment of precancerous conditions or reducing cancer risk, has further fueled this interest.

What Is Chemoprevention?

In the last decade, it has become clear that the definition of chemoprevention needs to include the concept of ‘delay’. This concept suggests that the preventive effects may have a limited duration. Even if the incidence of tumors eventually returns to the level observed in the untreated population, the rate of tumor development is reduced. As a result, many years or even decades can be added to a person's lifespan. Chemoprevention is a proactive approach to cancer management that focuses on using natural or synthetic substances to prevent, delay, or reverse cancer development. It involves identifying and utilizing specific agents or interventions that can interfere with the process of carcinogenesis, which is the transformation of normal cells into cancer cells. Chemotherapy drugs differ from those used for chemotherapy. Chemotherapy uses drugs to treat cancer, whereas chemoprevention makes an effort to prevent cancer by using drugs, vitamins, or other substances.

What Are the Strategies for Cancer Chemoprevention?

The three strategies involved in cancer chemoprevention include:

• Primary Chemoprevention:

  1. This prevention refers to interventions aimed at assisting healthy individuals in preventing the occurrence of a specific type of cancer. These individuals may possess high-risk characteristics, such as genetic mutations, that make them more susceptible to developing cancer.

  2. Medications, vitamins, and others are employed to prevent cancer in individuals who are currently in good health.

• Secondary Chemoprevention:

  1. It involves treatments targeted at premalignant lesions, such as colon adenomas, with the objective of halting their progression into cancer.

  2. Medications, vitamins, or other supplements are utilized to prevent a pre-cancerous condition from advancing to a full-blown cancerous state.

• Tertiary Chemoprevention:

  1. This prevention aims to assist patients who have previously been treated for cancer.

  2. Vitamins, medications, or supplements are administered to such individuals to reduce the chance of them developing another cancer in the future.

What Are the Mechanisms of Chemoprevention Agents?

Chemoprevention strategies can target various stages of tumor initiation, promotion, and progression. Researchers have identified numerous potential mechanisms and have attempted to categorize agents based on their effects on different phases of carcinogenesis. Many agents, particularly those with multiple targets derived from dietary origins, may impact the whole process of cancer development.

• Blocking Agents: Agents that prevent cancer initiation are commonly referred to as blocking agents. These compounds can work by preventing the interaction between chemical carcinogens or endogenous free radicals and deoxyribonucleic acid (DNA). By doing so, they reduce the level of damage and resulting mutations that contribute not only to cancer initiation but also to progressive genomic instability and overall neoplastic transformation. This protection can be achieved through various mechanisms, including:

  1. Reduction in the cellular uptake and metabolic activation of pro-carcinogens.

  2. Enhanced detoxification of reactive electrophiles and free radical scavenging.

  3. Induction of repair pathways.

  4. Reducing chronic inflammatory responses and suppressing the production of reactive oxygen and nitrogen species.

  5. Modulation of DNA methyl transferases to prevent or reverse hypermethylation-induced inactivation of tumor suppressor genes.

  6. Inhibition of histone deacetylases, which affects epigenetic mechanisms of carcinogenesis.

• Suppressing Agents: Once initiation has occurred, chemopreventive agents can influence the promotion and progression of initiated cells. These compounds are often referred to as suppressing agents. The major reported mechanisms contributing to their activity involve:

  1. Inhibition of signal transduction pathways, such as targeting nuclear factor (NF)-kappa B, to disrupt the effects of tumor promoters that would otherwise lead to cell proliferation.

  2. Blocking the promotion effect of hormones on tumor progression. For example, anti-estrogens like tamoxifen can counteract the promoting effect of hormones.

  3. Interfering with cancer cell metabolism and energy homeostasis by affecting certain pathways, which are potential targets for chemopreventive agents.

  4. Induction of apoptosis (programmed cell death) and inhibition of angiogenesis.

What Are the Different Chemopreventive Agents?

Here are some examples of chemopreventive agents:

• Phytochemicals: Phytochemicals are naturally occurring compounds found in plants that have been extensively studied for their chemopreventive properties. Examples include:

  1. Polyphenols: Resveratrol (found in grapes and berries), curcumin (found in turmeric), and epigallocatechin gallate (EGCG, found in green tea).

  2. Isothiocyanates: Sulforaphane (found in cruciferous vegetables like broccoli and cabbage).

  3. Carotenoids: Beta-carotene (found in carrots and other orange-colored fruits and vegetables), lycopene (found in tomatoes), and lutein (found in leafy green vegetables).

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs such as Aspirin, Ibuprofen, and Naproxen, commonly used as pain relievers, have shown chemopreventive potential due to their anti-inflammatory properties.

• Selective Estrogen Receptor Modulators (SERMs): SERMs are agents that selectively modulate estrogen receptors, often used for the prevention and treatment of hormone-related cancers. Tamoxifen and Raloxifene are examples of these agents that are used in breast cancer chemoprevention.

• Statins: Statins such as Atorvastatin, Simvastatin, and Rosuvastatin, primarily used to lower cholesterol levels, have been investigated for their potential chemopreventive effects, particularly in colorectal cancer.

• Retinoids: These compounds are derived from vitamin A and have shown chemopreventive effects, especially in skin cancers. Isotretinoin and Acitretin are examples of retinoids.

• Anti-estrogens and Aromatase Inhibitors: These agents target estrogen signaling and are used in the prevention and treatment of hormone-sensitive cancers, such as breast cancer. Examples include Anastrozole, Letrozole, and Exemestane.

• Vaccines: Vaccines have been developed to prevent specific viral infections that can lead to cancer. Examples include the human papillomavirus (HPV) vaccine and the hepatitis B vaccine.

• Proton Pump Inhibitors (PPIs): PPIs, commonly used to treat acid reflux and ulcers, have been studied for their chemopreventive effects in gastric and esophageal cancers. Examples include Omeprazole and Lansoprazole.

Conclusion:

The effectiveness and safety of chemopreventive agents are evaluated in great depth through clinical trials. Large groups of people with pre-cancerous lesions or a family history of cancer are frequently included in these trials because they are at a high risk of developing particular cancer. These studies evaluate the chemopreventive agents’ efficiency in lowering the occurrence or progression of cancer while keeping an eye out for any negative side effects. The outcomes of these studies shed important light on the applicability and impact of chemoprevention in clinical settings. In short, the prevalence of cancer in society can then be significantly reduced through the use of chemoprevention.