Dear Colleagues,

Compounds that prevent the initiation of premalignant lesions and their progression to malignancy are referred to as being cancer chemopreventive. To date, more than 1,000 substances have been evaluated and many were shown to prevent cancer. Several of these originated from dietary sources. Mechanistically, chemopreventive agents have been shown to exhibit both anti-tumor initiation and -tumor promotion effects. They inhibit tumor initiation by reducing the activity of enzymes involved in the metabolic activation of carcinogens into metabolites that produce DNA damage and/or by enhancing the activity of enzymes involved in carcinogen detoxification. In addition, they reduce oxidative damage to DNA and other cellular macromolecules by their ability to scavenge oxidative radicals. They inhibit tumor promotion/progression by multiple mechanisms such as reducing abnormal cell proliferation, inflammation, angiogenesis, tissue invasion and metastasis and promoting cell differentiation and programmed cell death (apoptosis). One interesting but poorly understood feature of chemopreventive agents is their ability to selectively inhibit the abnormal cells undergoing carcinogenesis, while not perturbing the normal cells. The most promising chemopreventive agents appear to be those which affect multiple cellular functions at doses that elicit little or no toxicity. Unfortunately, however, most chemopreventive agents that exhibit inhibitory activity in animal model tumor systems have been either ineffective or exhibited tumor promotional effects in humans.

In contrast, chemotherapeutic drugs are selected for use in cancer treatment largely by their ability to kill cancer cells either by direct damage to DNA and other cellular macromolecules or by targeting specific genes and their proteins in cellular signaling pathways. Chemotherapy is often used in conjunction with radiotherapy and/or with surgery in cases where surgery does not result in complete removal of the tumor. Recently, multiple studies are ongoing to evaluate the ability of chemotherapeutic drugs to enhance the effectiveness of immunotherapy for cancer treatment. Some tumor types appear to be treated quite effectively by immunotherapy.

Relatively few preclinical and clinical studies have evaluated the effects of using chemopreventive agents and chemotherapeutic drugs in combination for cancer treatment. In view of the wide range of cellular and molecular effects of chemopreventive agents, it seems logical that they could contribute significantly to the efficacy of chemotherapeutic drugs in cancer therapy. For example, chemopreventive agents might be expected to reduce the toxic effects of chemotherapeutic drugs on normal tissues. Similarly, the mechanisms described above by which they influence events in tumor promotion/progression would seem likely to add appreciably to the effectiveness of chemotherapy.  Thus, the purpose of this special issue in Pharmaceuticals is to identify some of the most promising chemopreventive agents and describe their mechanisms of action and to present some investigations that suggest the efficacy of using chemoprevention in combination with chemotherapy for cancer treatment.

Dr. John F. Lechner
Prof. Dr. Gary D. Stoner
Guest Editors

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• naturally- occurring chemopreventive agents
• cellular effects
• molecular effects
• chemoprevention + chemotherapy for cancer treatment