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The pursuit of molecular targets for cancer prevention and therapy

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Despite the intensive efforts and substantial advances that have occurred through focusing on improving treatments, cancer is still a leading cause of death worldwide. The World Health Organization (WHO) indicates that one third of all cancer deaths are preventable and that diet is closely linked to cancer ...

Despite the intensive efforts and substantial advances that have occurred through focusing on improving treatments, cancer is still a leading cause of death worldwide. The World Health Organization (WHO) indicates that one third of all cancer deaths are preventable and that diet is closely linked to cancer prevention. Based on this idea and numerous epidemiological findings, attention has centered on dietary phytochemicals as an effective intervention in cancer development. However, the failure of many large-scale clinical trials worldwide has raised doubts that diet-based cancer prevention can be clinically successful. Because these trials were not designed on mechanism-based preclinical studies, identifying cancer preventive dietary agents or functional foods that have specific molecular or cellular targets is thought to be essential to move forward. Every individual has a different and unique risk of cancer incidence, prognosis and response to treatment. Indeed, the necessity of personalized therapy for treatment of lung or breast cancer, for example, is well established. Such reports indicate a trend toward personalized cancer treatment as a requirement for effective cancer therapy. Conversely, a personalized diet for cancer prevention has not been as well documented, although prescribing a personalized diet for cancer prevention might make sense. Unfortunately, this will not likely happen anytime soon because beyond unhealthy eating and lack of exercise, a valid link between diet and cancer has been elusive.
On the other hand, owing to individual differences, a thorough analysis of distinct personal characteristics for the application of proper chemopreventive agents could be capable of providing health benefits especially in those at high-risk populations. Cancer prevention has been categorized into three main types that include primary (e.g., avoiding carcinogens), secondary (e.g., screening for premalignant lesions), and tertiary (e.g., preventing recurrence). Each type of cancer has its own particular characteristic genes and proteins that regulate its growth. Therefore, knowing the specific gene(s) or protein target(s) of a phytochemical chemopreventive agent increases the probability of the agent exerting efficacy in high risk individuals. Although, reports have suggested benefits and targets of phytochemicals, these reports mainly rely on cell and animal models. In order to apply phytochemicals as personalized cancer preventive agents, the effects of phytochemicals in humans will need to be assessed. In the future, personalized prevention methods using phytochemicals could play a crucial role in cancer prevention, especially in high-risk populations. Rigorous research in identifying molecular targets and conducting human studies with phytochemicals would provide an enhanced approach to personalized cancer prevention. Similar to the development of cancer therapeutic drugs, the development of the recent cancer preventive agents is based on the discovery of precise molecular targets. This research topic will focus on phytochemical-derived drug discovery and mechanisms by which these compounds can modulate distinct target proteins involved in oncogenic signaling. Phytochemicals, such as resveratrol (i.e., grapes, red wine), (-)-epigallocatechin gallate [EGCG] (i.e., green tea), [6]-gingerol (i.e., ginger), and many flavonoids (i.e., myricetin, kaempferol) have been reported to directly modulate numerous molecular signal transduction pathways and research efforts have centered on the effects of phytochemicals on signaling cascades known to induce cancer cell death or inhibit cancer cell proliferation.


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