Cancer has been a major challenge for public health in China. It ranks first among all causes of death in urban areas, and second in rural areas. This paper present the latest cancer statistics of China. The incident number of gastrointestinal cancers is still high and the burden of lung cancer and breast cancer are increasing. The trend indicates that the overall cancer burden would still be severe with the rapid development of China and aging population. Addressing this challenge requires comprehensive and multidisciplinary approaches. The current status of cancer control polices, structures, and cancer registration in China are described. National cancer control plans has been carried out by Ministry of Health since 1986. National program of cancer registry has been set up. In 2012, the number of population-based cancer registries has expanded to 222, covering populations with 200 millions. In areas with high risk of cancer, they have held systematic programs of cancer control. Many places such as Linzhou and Cixian have shown a down-trend of cancer incidence and mortality. The successful experiences in areas of high risk of cancer also promote the nationwide cancer campaign. The prevention programs include tobacco control, immunization against hepatitis B for infants and children, and cancer early detection and diagnosis. This paper provides considerable scope and motivation for future work on cancer control and prevention.

Contents
1 Introduction
2 Cancer statistics
3 The current status of cancer prevention and control
3.1 Strategies and policies for cancer control and prevention
3.2 Systematic construction for cancer related agencies
3.3 Cancer registry and surveillance
3.4 Experiences of cancer control in areas with high risk of cancer
3.5 Nationwide cancer control programs
4 Conclusion and outlook

We present a brief review of the history of chemoprevention of cancer, the present status of this field, and its prospects for the future. Topics covered are the scientific basis for chemoprevention of cancer, drugs in current use for chemoprevention of cancer, the need for new synthetic drugs, and the challenges ahead. The importance of the use of combinations of drugs for effective prevention is stressed.

Worldwide, breast cancer is the most common cancer in women, with 1.38 million breast cancer diagnoses cases estimated for 2008, accounting for 23% of all cancers in women. Breast cancer has the highest mortality rate of all cancers among women worldwide. Although technological advances in early detection and treatment have made inroads into these rates, breast cancer associated mortality remains high. Hence, interest has emerged in exploring approaches to preventing this disease and developing risk models to identify women most likely to benefit from preventive interventions. The current chapter addresses breast cancer risk-reducing agents that have progressed in their development to testing in phase Ⅲ clinical trials or in some cases to formal approval for a breast cancer risk reduction indication. The discussion here concentrates on agents targeting estrogen receptor (ER)-positive breast cancers, specifically selective ER modulators (SERMs) and aromatase inhibitors (AIs). The large phase III clinical trials assessing efficacy of these agents in breast cancer prevention are the focus, as these represent the gold standard in clinical testing and serve as the basis for approval of these anti-estrogens for risk reduction of breast cancer among high-risk women.

Consistent experimental, epidemiologic, and recent randomized controlled trial evidence demonstrates that aspirin lowers the risk of colorectal cancer (CRC). Prior expert bodies have recommended against the routine use of aspirin to prevent CRC in individuals at average risk, particularly in view of potential adverse consequences, including gastrointestinal bleeding. However, such recommendations preceded more recent high quality evidence of the benefit of aspirin for the prevention of not only colorectal cancer, but other cancers as well. This review summarizes this compelling body of evidence supporting the chemopreventive efficacy of aspirin. A broad anti-cancer effect of aspirin coupled with its potential role in the prevention of cardiovascular disease may tip the balance in favor of chronic aspirin use for many patients.

Primary liver cancer has been the leading cause of cancer death in Qidong, China, with about 800 deaths annually in this region of 1.1 million residents. Epidemiological studies have highlighted the importance of infection with hepatitis B virus (HBV) and dietary exposure to hepatocarcinogenic aflatoxins as key, interactive determinants of risk in Qidong and other endemic areas. Identification of these risk factors was enabled through the development of biomarkers allowing for measures of their prevalence in case-control and other study cohorts. Vaccination against HBV began in pilot studies in the 1980s in Qidong but did not become universal for newborns until earlier this decade. Despite minimal impact on cancer mortality to date, vaccination programs are poised to blunt the development of liver diseases including cancer in this region over the next generations. Strategies for reducing aflatoxin exposure are also required, especially for those already infected with HBV. We have conducted a series of proof-of-principle clinical trials in which drugs, dietary supplements and foods have been used to alter the metabolism and elimination of aflatoxins following unavoidable exposures. Using aflatoxin biomarkers as intermediate endpoints, the efficacy of these agents (oltipraz, chlorophyllin, broccoli sprout beverages) has been demonstrated, highlighting roles for frugal approaches to chemoprevention against environmental carcinogenesis. Remarkably, recent evidence garnered from retrospective analysis of archived serum samples from the past quarter century demonstrates a 40-fold drop in aflatoxin exposure in Qidong, likely driven by changes in the primary dietary staple from maize to rice. Thus, primary prevention, evoked by changing economic and agricultural policies in the 1980s, heralds the unanticipated promise of elimination of liver cancer from this endemic region in a fore-shortened timeframe.

Diet and nutrition are important modifiable and preventable risk factors for many chronic diseases including cancer. An up-to-date estimate indicated that about 1/5 to 1/3 of the world cancer burden are related to food, nutrition and physical activity and can be prevented or delayed. Nutritional intervention is an important strategy for cancer prevention and control. Since the 1980's, copious nutritional intervention studies have been carried out. Some studies showed the effectiveness of nutritional supplementation in reducing cancer risks. However, a larger number of studies failed to demonstrate such an effect, possibly because the populations were not deficient in the nutrients studied or the intervention was started too late. In the future, dietary and nutritional intervention studies on cancer should be carried out according to the nutritional statues and cancer patterns of different populations. At the same time, there is a great need for continually exploring cancer prevention through multinutrient or whole-food supplementations in a "green" chemoprevention approach. This is an important area for cancer research in China.

Contents
1 Introduction
2 Preventable cancer by healthy dietary and nutrition
3 Dietary and nutritional intervention strategies and measures
4 Nutrition chemoprevention
5 Food-based approach
6 Conclusions

Our laboratories have been evaluating a "food-based" approach to cancer prevention using black raspberries (BRBs) for the past 20⁺ years. Black raspberries contain multiple compounds with chemopreventive potential including vitamins A, C and E, selenium and calcium, numerous complex and simple polyphenols including anthocyanins, ellagitannins, quercetin, ferulic and coumaric acids, various carotenoids, and phytohormones such as β-sitosterol. Because BRBs are about 90% water, freeze-drying them concentrates these putative chemopreventive agents about 10-fold. Preclinical studies have shown that freeze-dried BRB powder inhibits the development of oral, esophageal, colon and breast tumors in animals. In humans, BRB powder exhibits chemopreventive effects on premalignant lesions in the oral cavity, esophagus and colon at dose levels that elicit little or no toxicity. BRBs function by reducing cell proliferation, inflammation and angiogenesis, and enhancing apoptosis, cell adhesion and differentiation. Molecular studies have identified multiple genes associated with these cellular functions that are protectively modulated by BRBs. Bio-fractionation studies suggest that most of the chemopreventive effects of BRBs are due to their content of polyphenols and fiber. It is likely that many other foodstuffs would exhibit protective effects if formulated in a manner similar to that described for BRBs.

Constituents from food, beverages and medicinal herbs have been studied extensively as cancer preventive agents. This article uses vitamin E (a nutrient) and tea polyphenols (non-nutritive phytochemicals) as examples to illustrate the opportunities, problems and lessons learned in this research area. The hypothesis that vitamin E prevents cancer is derived from epidemiological observations, but large scale human intervention trials with α-tocopherol (the most commonly recognized form of vitamin E) produced disappointing results due to our lack of understanding of the biological activities of different forms of tocopherols. The hypothesis that green tea prevents cancer has strong supportive evidence from laboratory studies, but only limited evidence from human studies. Even with these inconsistencies, many important advances have been made and lessons learned in the field of cancer prevention by phytochemicals. In future studies, more integration of laboratory and human studies are needed to advance the field of cancer chemoprevention.

Carcinogenesis is a multistage process involving hundreds of genes and gene products that regulate various cellular functions. The prevailing opinion today is that cancer might be prevented with small molecules that target specific or multiple cancer genes, signaling proteins and transcription factors. Some promising small molecule inhibitors include various dietary factors. Many of these factors appear to act on multiple tumor-associated cellular pathways with potent anticancer activity, low toxicity and limited adverse side effects. Combining agents or using individual agents that target multiple pathways is a strategy that is gaining acceptance. Powerful modern technologies are needed to accelerate the process of drug discovery especially to find compounds that can suppress multiple cellular signaling pathways. Combining supercomputer technologies, such as in silico screening, with protein structure determination and experimental laboratory validation assays to identify multiple protein targets of anticancer compounds is an example of technologies needed. This paper highlights two of the signaling pathways known to play an important role in carcinogenesis and describes the computational strategies used to identify small molecule inhibitors of these pathways. Finally, examples of molecules and their protein targets, which have been identified and validated by these combinational strategies for chemoprevention, are presented.

Next generation sequencing (NGS) has been widely used in identifying the most important driver genes to lung carcinogenesis. Compared to the traditional sequencing approaches such as Sanger sequencing, NGS has several distinct advantages including the capacity to fully sequence almost all of the genes in the whole genome, whole exome or whole transcriptome, and the ability to simultaneously detect all types of genetic variants such as base substitutions (mutations), insertions, deletions, copy number variants, structural variants, gene fusions, etc. In the past few years, several comprehensive NGS studies on three major types of lung cancer (lung adenocarcinoma, squamous cell lung cancer, and small-cell lung cancer) have been successfully conducted which both confirmed the significance of the previously identified lung cancer driver genes and revealed the ‘novel’ significant driver genes that were not well known in the lung cancer context before. Functional somatic genetic alterations in these genes exist in the majority of the lung cancer samples studied and altered the critical pathways whose aberrations have a direct impact on lung cancer development. It is anticipated that the expanding list of lung cancer driver genes will provide unprecedented opportunities to identify the best targets for lung cancer prevention and treatment.

Cancer is one of the leading causes of death worldwide. The innovation of modern diagnostics and chemotherapeutics has improved cancer patients' treatment and care, but advanced stages of cancer remain extremely challenging to treat. Therefore, new and creative approaches are needed to prevent and treat cancer. Herbal medicines have been used for many centuries to prevent diseases such as cancer. Funding agencies, such as the National Cancer Institute in the United States, have recently emphasized support for cancer chemoprevention research using natural phytochemicals and non-toxic drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent or delay the onset of cancer. This perspective distills the latest in cancer chemoprevention research using bioactive components from fruits, vegetables, green tea and Traditional Chinese Medicines (TCM), focusing on Nrf2, epigenomic and cancer stem cell effects.

The nuclear factor erythroid-2 related factor 2 (Nrf2) is a pivotal activator of genes encoding cytoprotective and detoxifying enzymes that protect against oxidative and eletrophilic stress. Under normal condition, Nrf2 is localized in the cytoplasm binding to Kelch-like ECH-associated protein 1 (KEAP1), which facilitates the degradation of Nrf2 via the ubiquitin proteasome pathway. Under stress conditions, oxidants or electrophiles abrogate the interaction between KEAP1 with Nrf2, resulting in increased nuclear accumulation of Nrf2 and the transcriptional induction of target genes. Activation of Nrf2 pathway is crucial for cancer chemoprevention. However, over-expression of Nrf2 has been found in many types of cancer, facilitating tumor growth and resistance to anticancer therapy. This article summarises recent progress in understanding the regulation of Nrf2 activity, and the new development in finding small molecules modulating Nrf2/ARE signalling pathway.

Contents
1 Introduction
2 Dual roles of Nrf2 in carcinogenesis
2.1 Activation of Nrf2 is important for cancer chemoprevention
2.2 The dependence of tumour cells on Nrf2
3 The complexity of Nrf2 signaling
3.1 KEAP1-independent Nrf2 degradation
3.2 p21 activates Nrf2 through direct interacting with NRF2
3.3 p62 activates Nrf2 through interacting with KEAP1
3.4 Oncogenes activate Nrf2
3.5 Nuclear receptors inhibit Nrf2 activity
4 Small molecules modulate Nrf2/ARE signalling pathway
4.1 The methods used for identifying novel Nrf2 activators
4.2 The Nrf2 inhibitors
5 Concluding remarks

Natural products hold great promises for being developed into chemopreventive drugs due to their low toxicity and high accessibility. However, poor oral bioavailability limits the biological effects of many natural products in vivo. This paper reviews the factors that affect the bioavailability of several classes of important chemopreventive natural products including resveratrol, curcumin, berberine, genistein, quercetin, allium compound, and ginsenoside compound K. The up-to-date research data suggested that membrane permeability, solubility, and metabolism are the primary factors that limit the oral bioavailability of these natural products although chemical and microbial stability may also contribute to the problem. An important direction for future investigation is to further optimize the oral bioavailabilities of these natural products and realize their chemopreventive and chemotherapeutic effects in vivo.

Since Helicobacter pylori was identified in early 1980's, evidences accumulated reveal that infection with Helicobacter pylori could cause gastric ulcer, chronic inflammatory of gastric mucosa and increased the risk of gastric cancer. Because the risk for gastric cancer attributable to Helicobacter pylori infection is as high as 40—60%, anti-Helicobacter pylori is a critical strategy in primary prevention of gastric cancer, particularly in the high-risk population. The epidemiology, biology, therapy of Helicobacter pylori infection and gastric cancer prevention by eradication of Helicobacter pylori are reviewed in this article.

Chronic infection attributes to 29.7% of cancer mortality in China, among which Helicobacter Pylori (HP), Hepatitis B virus (HBV), and Human papillomavirus (HPV) are the three major infectious agents. HBV vaccine and HPV vaccine were respectively developed in 1981 and 2006, and have been proven could efficiently prevent HBV-related hepatocarcinoma and HPV-related cervical cancer. In May of 2012, "China Chronic Disease Prevention and Control Work Plan (2012—2015)" was promulgated. This work plan not only requires exploring appropriate screening technologies for major cancers in high-risk areas, and also requests strengthening the implementation of HBV vaccination and HPV vaccination among high-risk population. Moreover, China announced to have successfully developed HP vaccine recently, which could efficiently prevent HP-related gastric cancer. By summarizing the current research progress of the three anti-cancer prophylactic vaccines, this review made a brief introduction of the great breakthroughs in cancer primary prevention. Furthermore, it also reviewed the implementation history of HBV vaccine in China, and the current gap existing between developed countries and China for HPV vaccine. This review hopes to help Chinese policy makers further improve and complete the HBV vaccination program, to accelerate the launch of HPV vaccination program with the least delay, and to introduce the HP vaccine at appropriate time in China.

Contents
1 Introduction
2 Hepatitis B virus (HBV) vaccine
3 Human papillomavirus (HPV) vaccine
4 Helicobactor Pylori (HP) vaccine
5 Perspective

Activating the immune system for therapeutic benefit in cancer has long been a goal in immunology and oncology. After decades of disappointment, the tide has finally changed due to the success of recent proof-of-concept clinical trials. Most notable is the ability of the anti-CTLA4 antibody, ipilimumab, to achieve a significant increase in survival for patients with metastatic melanoma, for which conventional therapies have failed. In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses together with the advent of targeted therapies, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.

Contents
1 Introduction
2 Cancer vaccines are finally showing early signals of activity
3 An efficacious cell-based vaccine for prostate cancer
4 Combination immunotherapy
5 Recalling the use of vaccines
6 Perspective

Anti-tumor B (ATB) is a Chinese herbal mixture of six plants (Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus and Dioscorea bulbifera). ATB is also called Zeng Sheng Ping (ZSP). Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal cancer, mostly squamous cell carcinomas. The chemopreventive effects of ATB on the development of 4-nitroquinoline-1-oxide (4NQO) induced oral squamous cell carcinomas in A/J mice were systematically evaluated and it was found that ATB reduced 4NQO-induced oral cancer development by approximately 60%. Similar results were also seen in 7,12-dimethylbenz(a)anthracene (DMBA) induced oral cancer in hamsters. A randomized clinical trial was conducted in patients with oral leukoplakia. Treatment with ATB (4 tablets, 3 times per day for 8—12 months) reduced the size of oral lesions in 68% of the patients versus 17% of the patients in the placebo control group (P < 0.01). These results indicate that ATB may be a potent chemopreventive agent against the development of oral cancer in humans.

The human gut harbors trillions of microbes that function as a multi-cell organ. This microbial community appears to cluster in certain types regardless of its vast number and complexity. The gut microbiota plays a key role in the host physiology since it is involed in energy breakdown, multiple host metabolic pathways, signaling, immune system balance etc. The microbiota codevelop with the host and is subject to pertubation and resilience. Changes in the composition of the gut microbiota have been associated with diverse, complex diseases including inflammatory bowel disease, metabolic disease and cancer. Therefore, microbiota-targeted early diagnosis and therapy may become possible in the near future, especially in the chemoprevention of cancer.