Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.
Cancer now affects as many as 24 million people worldwide, and results in over six million deaths each year [
It is now well established that solid tumor growth is dependent upon angiogenesis, the growth of new blood vessels [
Antiangiogenic therapy has been validated as an effective cancer treatment strategy for a growing number of cancer types, including colorectal, renal, liver, lung, brain, pancreatic neuroendocrine tumors (NET), gastrointestinal stromal tumors (GIST), multiple myeloma, and myelodysplastic syndrome [
The human body contains 60,000 miles of blood vessels, including 19 billion capillaries. All normal cells in the body are located no further than 100–200
More than 30 endogenous molecules have been identified as angiogenic factors (Table
Angiogenic factors.
Angiogenin | |
Angiopoietin-1 | |
Adrenomedullin | |
Del-1 | |
Fibroblast growth factor-1 (acidic FGF, FGF1) | |
Fibroblast growth factor-2 (basic FGF, FGF2) | |
Follistatin | |
Granulocyte-colony-stimulating factor (G-CSF) | |
Hepatocyte growth factor/scatter factor (HGF/SF) | |
Interleukin-3 (IL-3) | |
Interleukin-8 (IL-8) | |
Intermedin | |
Keratinocyte growth factor (FGF-7) | |
Leptin | |
Midkine | |
Neuregulin | |
Osteogenic protein-1 | |
Placental growth factor (PlGF) | |
Platelet-derived endothelial-cell growth factor (PD-ECGF) | |
Platelet-derived growth factor (PDGF) | |
Pleiotrophin | |
Progranulin | |
Proliferin | |
Transforming growth factor- | |
Transforming growth factor- | |
Tumor necrosis factor- | |
Vascular endothelial growth factor/vascular permeability | |
factor (VEGF/VPF) |
Angiogenesis inhibitory activity was first discovered in studies of cartilage, a naturally avascular tissue [
A separate and distinct class of inhibitors is comprised of proteolytic fragments derived from cleaved larger molecules. Angiostatin is an internal fragment of plasminogen and specifically inhibits endothelial cell proliferation [
Endogenous inhibitors of angiogenesis.
Angiopoietin-2 (in the absence of VEGF) | |
Angiostatin | |
Antithrombin III fragment | |
Arresten | |
Canstatin | |
Chondromodulin I | |
Connective tissue growth factor (CTGF) | |
Decorin | |
Endorepellin | |
Endostatin | |
Fibronectin 20-kDa fragment | |
Interferons- | |
Interleukin-4 (IL-4) | |
Interleukin-10 (IL-10) | |
Interleukin-12 (IL-12) | |
Interferon-inducible protein-10 (IP-10) | |
Kringle 5 | |
Metastatin | |
METH-1 | |
METH-2 | |
2-Methoxyestradiol | |
Osteopontin cleavage product | |
PEX | |
Pigment epithelium-derived factor (PEDF) | |
Plasminogen activator inhibitor (PAI) | |
Platelet factor-4 | |
Prolactin 16-KDa fragment | |
Proliferin-related protein | |
Prothrombin kringle 2 | |
Maspin | |
Restin | |
Soluble fms-like tyrosine kinase-1 (S-Flt-1) | |
SPARC cleavage product | |
Tetrahydrocortisol-S | |
Tissue inhibitors of matrix metalloproteinases (TIMPs) | |
Thrombospondin-1 and -2 | |
Transforming growth factor- | |
Troponin-1 | |
Tumstatin | |
Vascular endothelial growth inhibitor (VEGI) | |
Vasostatin |
Vascular growth is physiologically governed by a homeostatic balance between positive and negative angiogenesis regulators, so that neovascularization is normally suppressed [
Genetic control of angiogenesis.
Id1 p53 | |
Id3 Rb | |
HIF-1a VHL | |
K- | |
N- | |
c- | |
c- | |
c- | |
c- | |
c- | |
HER2/ | |
EGFT | |
Raf | |
Mek | |
p73 | |
Del-1 | |
FzD | |
Bcl2 | |
MDNM2 | |
PML-RAR | |
ElF-4E |
Microscopic cancer cells are commonly present in the healthy adult, the result of errors during replication of 60–90 trillion cells. To acquire sustenance, the incipient tumors (60–80 cells) may migrate toward existing host vessels, a process known as vessel cooption, but their growth remains limited [
Autopsy studies have shown that these microscopic cancers are present in the breasts of up to 40% of women between the ages of 40 and 50 years, and in 50% of prostates in men between 50 and 60 years. By age 70, microscopic cancers are detected in the thyroids of virtually everyone. Most of these tumors never become clinically significant, leading to the concept of “cancer without disease” as a normal state during aging. Physiological angiogenesis inhibition is regarded as one of the mechanisms that prevent microscopic cancers from converting to a malignant phenotype.
To expand beyond the limits of the preexisting vascular supply, tumors recruit new blood vessels from surrounding vessels, an event known as the “switch” to the angiogenic phenotype [
The switch to the angiogenic phenotype occurs during multistage tumorigenesis. As malignancy develops, cells progress from a prevascular stage (normal to early hyperplasia) to a vascular stage (late hyperplasia to dysplasia to invasive carcinoma). Angiogenesis becomes clearly evident during dysplasia and is critical for further growth. Targeting tumor angiogenesis may be a novel strategy for preventing cancer. (Reprinted by permission from the Angiogenesis Foundation. Copyright 2011 by The Angiogenesis Foundation. All rights reserved).
In a model of spontaneous
A second study utilized the bovine papillomavirus oncogene in a transgenic mouse model of dermal fibrosarcoma [
A third study involved K14-HPV16 transgenic mice in which the human papillomavirus (HPV) type 16 oncogene is targeted to expression in basal cells of the epidermis by regulatory elements of the human keratin-14 promoter [
Together, these data demonstrate that angiogenesis is a discrete, genetically regulated and rate-limiting step during multistep tumorigenesis, that the transition from prevascular to vascular phase is accompanied by the production and release of one or more angiogenic growth factors, and that host inflammatory cells may amplify the angiogenic switch by contributing additional stimuli.
The onset of angiogenesis precedes an exponential phase of tumor growth accompanied by local organ invasion. The velocity of angiogenic capillary growth ranges from 0.223 to 0.8 mm/day [
The concept of “antiangiogenesis” was first proposed in 1971 by Judah Folkman, who hypothesized that inhibition of neovascularization at an early stage of cancer development could prevent tumor growth and metastases and maintain tumor dormancy [
Specific molecular and cellular targets have been identified for tumor angiogenesis. These include targets present during the orderly events characterizing new blood vessel growth [
The clinical development of antiangiogenic therapy began in the late 1980s. The first successful treatment of a vascular tumor (pulmonary hemangiomatosis) occurred in 1989 using interferon-
Approved antiangiogenic agents and cancer indications.
Bevacizumab (Genentech/Roche) | |
Cetuximab (Bristol-Myers Squibb/Imclone) | |
Endostatin (Simcere)† | |
Erlotinib (Genentech/Roche/OSI) | |
Everolimus (Novartis) | |
Imiquimod (Graceway/3M) | |
Interferon alfa (Roche/Schering) | |
Lenalidomide (Celgene) | |
Pazopanib (GlaxoSmithKline) | |
Sorafenib (Bayer/Onyx) | |
Sunitinib (Pfizer) | |
Temsirolimus (Wyeth) | |
Thalidomide (Celgene) | |
Vandetanib (AstraZeneca) |
†Available only in China.
Source: Angiotracker, The Angiogenesis Foundation (
Collectively, translational research studies have shown that overall disease burden is important to consider in the evaluation of the clinical effects of any antiangiogenic agent. Advanced cancers contain well-established, extensive vascular networks that may respond minimally to angiogenesis inhibitors. Vascular destructive agents, also known as vascular targeting agents, may be required to achieve a clinically significant effect on tumor perfusion [
The remainder of this paper is devoted to discussing the potential for angiogenesis inhibitors for prevention of cancer.
Angiogenesis inhibition offers an opportunity to interrupt an early, rate-limiting step in tumorigenesis [
Animal studies have demonstrated that early administration of angiogenesis inhibitors is highly efficacious. The drug TNP-470 (
The effect of TNP-470 on subclinical disease has also been elegantly studied by Shusterman and colleagues [
Cancer chemoprevention is defined as the use of pharmacological, natural, or dietary agents to inhibit the development of invasive cancer by blocking DNA damage caused by carcinogens or by arresting the progression of premalignant cells after damage has already occurred [
Chemopreventive agents that possess antiangiogenic properties.
Alpha-difluoromethylornithine (DFMO) | |
Aspirin | |
Brassinin | |
Celecoxib | |
Curcumin | |
1 | |
Ellagic acid | |
Epigallocatechin 3-gallate | |
Finisteride | |
Genistein | |
Naringenin | |
Oltipraz | |
Resveratrol | |
Retinoids | |
Selenium | |
Silymarin | |
Statins | |
Sulindac | |
Tamoxifen |
Source: Angiotracker, The Angiogenesis Foundation (
After water, tea is the second most popular liquid in the world, and its consumption is linked with a decreased risk of colon, prostate, lung, esophageal, and other cancers [
The molecular mechanism of EGCG is the result of its inhibition of urokinase and two gelatinases (MMP-2 and -9) involved in vascular as well as tumor invasion [
Preliminary data from these trials suggest clinical efficacy. An Italian study involving men with high-grade prostate intraepithelial neoplasia (HGPIN) demonstrated a protective effect from consuming daily green tea catechins over the course of a single year [
Polyphenon E, an extract from green tea leaves containing a defined mixture of polyphenolic catechins, is in clinical trials for prostate, bladder, esophageal, lung, head and neck cancers, and leukemia. In topical form, Polyphenon E 15% ointment was approved by the U.S. FDA in 2006 as a treatment for external genital warts, which is considered an angiogenic neoplasm and a precursor to cervical cancer [
Genistein (4′,5,7-trihydroxyisoflavone), an isoflavonoid found in soybeans, has both chemopreventive and antiangiogenic activity. It suppresses carcinogenesis in a variety of animal models of mammary and prostate carcinoma following oral and parenteral administration [
The antiangiogenic activity of genistein was initially detected in a study of healthy Japanese individuals who consumed a traditional soy-rich Japanese diet [
Such clinical studies have helped dispel the theoretical concerns that soy intake may worsen breast cancer or interact with tamoxifen treatment due to the fact that genistein is a phytoestrogen. In fact, among women with breast cancer, soy food consumption has now been shown in numerous, large-scale studies to be significantly associated with decreased risk of death and recurrence, regardless of estrogen receptor status or tamoxifen use [
Resveratrol (3,4′,5-trihydroxystilbene) is a natural phytoalexin and polyphenol found in more than 72 plant species, such as mulberries, peanuts, grapes, and grape products, including red and rose wine. Fresh grape skins contain 50–100
Red wine in particular has been repeatedly shown to have protective effects in large population studies. The California Men’s Health study of over 84,000 men demonstrated an inverse relationship between red wine consumption and lung cancer incidence. Notably, there was a 61% risk reduction for men drinking at least one glass of red wine per day [
Lycopene, a type of natural pigment in the carotenoid family, gives tomatoes and other fruits such as watermelon and papayas their bright red color. Lycopene is an angiogenesis inhibitor which suppresses signaling by PDGF and Platelet Activation Factor
Two interventional studies have also demonstrated potent biologic effects of lycopene in the setting of malignancy. In one study, 32 men who were recently diagnosed with early-stage prostate cancer were instructed to eat one meal per day incorporating commercially made tomato sauce containing 30 mg of lycopene for 3 weeks. They then underwent curative prostatectomy; pathologic examination of the resected tissue showed a 3-fold increase of lycopene concentration in the prostate tissue, along with a slight decrease in blood prostate-specific antigen (PSA) level [
In the Health Professionals Follow-Up Study of over 51,000 men, the highest quintile of lycopene consumption was found to have a 15% risk reduction for developing prostate cancer compared to men in the lowest quintile [
Omega-3 fatty acids are unsaturated fatty acids that are vital for normal metabolism but cannot be synthesized by the human body. The best known sources of the long-chain omega-3 fatty acids—docosahexaenoic acid (DHA) and eicosapentaenoic (EPA)—are cold water oily fish such as salmon, herring, mackerel, anchovies, sardines, and trout. Both preclinical and epidemiological studies suggest that omega-3 PUFAs are effective cancer preventative agents. Omega-3 PUFAs inhibit angiogenesis by downregulating angiopoietin-2 and may competitively inhibit the bioconversion of omega-6 PUFA's into their angiogenesis-promoting derivatives such as prostaglandins and arachidonic acid [
Intake of omega-3 PUFAs from seafood has been associated with a decreased risk for certain cancers, including pancreatic, colon, breast, and prostate cancer. In a case-control study of 532 people diagnosed with pancreatic adenocarcinoma, consumption of omega-3 fatty acid of at least 0.85 g/day was associated with a decreased risk of pancreatic cancer; those with the highest intake had a 30% risk reduction [
Cruciferous vegetables—which include cabbage, broccoli, cauliflower, collard greens, mustard greens, radishes, Brussel sprouts, bok choy, and kale—are rich in glucosinolates, a mustard oil glycoside that imparts a spicy, bitter flavor. The enzyme myrosinase—stored in a separate compartment of the plant cell and liberated when the plant is crushed—converts glucosinolate to the bioactive molecules isothiocyanate and indole-3-carbinol, both of which are antiangiogenic. Sulforaphane, a type of isothiocyanate, acts through inactivation of hypoxia inducible factor-1 alpha, activation of FOXO transcription factors, and promotion of endothelial cell apoptosis [
Epidemiological evidence suggests that regular dietary intake of cruciferous vegetables may lower the risk of developing several cancers. A major prospective dietary study, the European Prospective Investigation into Cancer and Nutrition (EPIC), followed the dietary habits and health of 521,468 subjects in 10 European countries between 1991–2000 [
Another large prospective study of more than 35,000 women living in Iowa and followed for 20 years found a 18% reduced risk for non-Hodgkin’s lymphoma (NHL) among women who had the highest consumption of cruciferous vegetables; in particular, consumption of at least 4 servings/month or broccoli was associated with a 28% risk reduction for non-Hodgkin’s lymphoma [
Flavonoids are a family of polyphenols that serve as important plant pigments. Their natural roles may include acting as photoprotectants, antimicrobials, deterrents against herbivores, as well as attractants to pollinators and seed dispersant animals. They are subcategorized by chemical structure into flavones, flavonols (such as quercetin), anthocyanidins, proanthocyanidins, ellagic acid, ellagitannins, and isoflavones (such as genistein mentioned earlier), among others. In contrast, the term flav
Flavonoids in fruits and vegetables include quercetin, anthocyanidins, proanthocyanidins, ellagitannins, among others. Flavonoids are antiangiogenic through a variety of mechanisms; they inhibit VEGF expression, inhibit endothelial cell migration, and decrease matrix metalloproteinases MMP-2 and MMP-9 [
Quercetin is a flavonoid found in numerous types of fruits and vegetables. Its antiangiogenic properties include inhibition of MMP-2 and MMP-9 secretion from tumor cells and inhibition of endothelial cell proliferation and migration [
One of the richest sources of dietary flavonoids is red onion, which has particularly high levels of quercetin. Case control studies from Italian and Swiss populations have shown that moderate (1–7 servings/week) to high frequency (>7 servings/week) of onion consumption protects against a variety of cancer including colorectal, prostate, ovarian, and laryngeal cancers [
Anthocyanins are pigments that are present in many types of berries and grapes as well as red wine. They exhibit a purple color at neutral pH, red in acidic, and blue in alkaline conditions. Anthocyanins are end-products of the flavonoid pathway, while anthocyanidins are their aglycone precursors. Their natural function may be to attract pollinators and animals to eat the fruit or plant and disperse their seeds.
They have been shown to inhibit angiogenesis and tumor growth in experimental animals injected subcutaneously with N-nitrosomethylbenzylamine (NMBA), an esophageal carcinogen [
An extract from black raspberries has been studied in human subjects diagnosed clinically with oral intraepithelial neoplasia. BRB 10% was applied in a gel form to the oral mucosa four times daily. After 6 weeks, there was reduced histological grade of dysplastic lesions in 50% of treated subjects, and reduced levels of COX-2 and iNOS in the lesions [
Proanthocyanidins are a type of tannin—large polymeric chains of flavonoids—found in many plants and fruits, notably cacao, cinnamon, cranberry, apples, grapes, black current, chokeberry, and persimmon. Proanthocyanidins are thought to be the major source of flavonoids ingested in the Western diet [
Proanthocyanidins constitute 60% of the polyphenol content in cacao, the source of chocolate [
There is evidence that cacao consumption can affect human vasculature and health. After ingestion, cacao flavonoids are stable in the gastric environment and can be detected in human plasma [
Procyanidins are also found in cinnamon, which have been found to inhibit angiogenesis and tumor growth. Cinnamon extract inhibits VEGF receptor-2 on endothelial cells and suppresses endothelial cell proliferation, migration, and tube formation
Many edible berries also contain proanthocyanidins, including the American cranberry, black currants, and grapes. Chokeberries, named because of their extreme astringency, contain among the highest levels of proanthocyanidins detected [
Both apples and apple juice are rich sources of procyanidins in addition to other polyphenols previously described such as quercetin and catechins. Based on the USDA Continuing Survey of Food Intakes by Individuals (CSFII), apples are a major source of proanthocyanidins in the U.S. diet [
Epidemiological studies have provided accumulating evidence that apples have cancer-preventive properties, particularly against lung and colorectal cancers. In the Nurses Health Study involving 77,000 women, a statistically significant 37% risk reduction for lung cancer was observed among women for increases of 1 serving per day of apples or pears [
Ellagitannins are glycosides of the flavonoid ellagic acid and fall under the category of hydrolyzable tannins. They can be found in numerous types of fruits and nuts including pomegranate, strawberries, blackberries, raspberries, muscadine grapes, walnuts, and pecans [
All parts of the pomegranate contain high levels of ellagitannins, of which the primary type is punicalagin. Bioactive polyphenols are found not only in the edible aril (pulp and seed) which is popularly consumed, but also concentrated in the peel of the fruit, which is not usually consumed but may be part of the juice extraction by some processors. Indeed, polyphenol extraction increases 6.5-fold when the whole fruit is processed compared to juice from arils alone [
A form of vitamin K, menaquinone (vitamin K2), found in certain food sources is antiangiogenic and associated with a reduced risk for developing several forms of cancer. Menaquinone is distinct from the phylloquinone (Vitamin K1) present in dark leafy vegetables. Instead, menaquinone is a fat—soluble vitamin formed naturally by bacteria in fermented dairy products, including cheese and yogurt, in fermented soy such as natto, and also present in dark meat. Certain cheeses, such as Dutch Gouda, Swiss Emmental, and Norwegian Jarlsberg, have particularly high concentrations of menaquinone. In laboratory studies, menaquinones suppress angiogenesis, enhance tumor apoptosis, and inhibit the proliferation of cancer cells [
A subpopulation of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, called the Heidelberg cohort, followed the diet and health status of more than 24,300 participants for at least ten years, starting in 1994. The participants answered detailed questionnaires at regular intervals about their diet and general health. During the follow-up period, 1,775 cancer cases were diagnosed, of which 458 were fatal. Among the foods documented, participants who consumed the most cheese (at least 41 g/day) had a significantly reduced risk of dying from cancer compared with those who consumed the least (less than 14 g/day) [
Prospective clinical studies of vitamin K2 have shown chemopreventive activity in patients. In a study of 40 women in Osaka diagnosed with viral liver cirrhosis, individuals were assigned randomly to an intervention or control group. During more than 7 years of followup, the cumulative proportion of people who developed hepatocellular carcinoma (HCC) was significantly smaller in the group that received vitamin K2 (45 mg/day) [
Curcumin (diferuloylmethane), a flavonoid derived from the plant
A Phase I prevention trial of curcumin (500–800 mg/day) showed histological improvement of lesions in patients with various malignant and premalignant lesions, including recently resected bladder cancer, oral leukoplakia, intestinal metaplasia, CIN, and Bowen’s disease [
Beta-cryptoxanthin is a natural carotenoid pigment present in brightly colored orange, red, or yellow foods. Structurally it is related to beta-carotene, and is ultimately metabolized to vitamin A in the body and can be found circulating in the blood after consuming carotenoid-rich foods. Vitamin A and retinoic acid analogs are antiangiogenic and synthetic derivatives have been investigated as chemopreventive agents [
Papaya is a rich source of carotenoids, with the same lycopene content as tomatoes, but twice the beta-cryptoxanthin content. Studies in tropical populations have shown that increased daily consumption of papayas results in higher levels of beta-cryptoxanthin in the blood [
Other studies have shown a risk reduction with the consumption of papaya and carotenoid-rich fruits for other cancers, including lung and gall bladder cancers [
In a study of women, diet, and breast cancer risk, 403 breast cancer cases and 602 controls from the Nurses' Health Study were examined for high breast densities, a strong predictor for breast cancer risk [
We have identified antiangiogenic activity in a number of other dietary-derived chemopreventive molecules. These include brassinin, a phytoalexin found in Chinese cabbage; the citrus-derived bioflavonoids hesperidin and naringenin; ellagic acid from berries, pomegranate, and grapes; silymarin from milk thistle and artichoke; and the organosulfur allyl disulfide derived from garlic [
The diverse natural sources of these and other antiangiogenic chemopreventive molecules raise the possibility of designing scientific diets for patients at high risk for cancer, or for those with known disease to chronically suppress angiogenesis and tumorigenesis.
Angiogenesis is a critical, rate-limiting step in the development of all known cancers, and its inhibition suppresses tumor growth, progression, and metastases. Antiangiogenic therapy represents a new approach to the early intervention and prevention of malignant disease. During the next two decades, the total yearly number of newly diagnosed cases of cancer is projected to rise from 12.4 million new cases per year in 2008 to 26.4 million in 2030, and the number of annual deaths is projected to increase 170%, to 17 million [
The identification of dietary sources of antiangiogenic molecules has been aided tremendously through observational epidemiologic studies, which have the ability to identify specific foods associated with reduced cancer risk. These studies generally fall under the categories of prospective cohort and retrospective case-control studies, and more of both of these types of studies will be necessary to identify additional sources of antiangiogenic compounds and to help confirm the chemopreventive properties of previously identified foods and their constituent bioactive molecules.
The dietary prospective cohort study allows thorough assessment of dietary exposures with a reduced risk of recall bias as patients are initially cancer-free when enrolled. As study participants are followed into the future and observed for the development of cancer and other cancer-related endpoints, investigators can identify specific foods present in participants’ diets that are associated with cancer risk reduction. With the evolving understanding of the underlying molecular basis of various naturally antiangiogenic foods, an important consideration for future cancer prevention cohort studies will be to ensure accurate assessment of participants’ dietary intake of bioactive compounds. This will include not only comprehensively querying participants about all potential dietary sources of the bioactive compounds of interest, but also obtaining more detailed information about the preparation of foods, as this can significantly impact the amount of antiangiogenic molecules obtained through diet. Furthermore, the subtypes of foods consumed, such as the specific variety of apple or tomato eaten by a participant, and the way the food is processed or cooked prior to consumption, can strongly affect the amount of consumed bioactive molecules and would be important information to collect. Thus, while the food frequency questionnaires (FFQs) used in past cohort studies have attempted to quantify the intake of various foods, future studies focused on antiangiogenesis may be able to make a more detailed and accurate assessment of this particular aspect of dietary intake.
Case-control studies can also be valuable as a method for expediently identifying promising dietary exposures without the need for the long timeframes and massive study populations that typically characterize dietary cohort studies. While case-control studies are nearly always vulnerable to recall bias on the part of the cancer patients who compose the case populations, they are a valuable starting point in identifying promising risk-reducing foods that can be further explored through prospective and, more recently, interventional dietary studies. The key to these studies will be the use of well-designed dietary survey instruments and methods to allow data capture on short time horizons that can accurately gauge the intake of antiangiogenic and chemopreventive biomolecules. Finally, interventional dietary studies are a particularly promising methodology with which to confirm the antiangiogenic and chemopreventive properties of specific foods and bioactive molecules. In particular, recently diagnosed cancer patients or those with pre-invasive angiogenesis-dependent lesions such as colonic adenomas, prostatic intraepithelial neoplasia, cervical intraepithelial neoplasia, and actinic keratoses could potentially show significant benefit from short-term antiangiogenic dietary interventions with regards to progression, metastasis, or recurrence of their lesions [
The United States Department of Agriculture’s update to its longstanding
Data and conclusions from rigorous dietary cancer prevention studies should be implemented into public health policy. Optimal health outcomes result not just from high quality medical care, but also from diet and lifestyle patterns that can intercept disease at the earliest microscopic stages. Investments in cancer prevention, guided by the biological principles of antiangiogenic therapy, will expand on the substantial clinical applications already established by the biopharmaceutical industry. Cancer prevention using antiangiogenic factors present in widely available foods further offers an egalitarian strategy for large populations in societies that increasingly recognize the value of health-promoting dietary choices. Many dietary sources of angiogenesis inhibitors are common ingredients in the world's most popular culinary traditions (i.e., Asian, Mediterranean, etc.). We propose that an antiangiogenic diet is a practical and cost-effective method to reduce the risk of cancer and other diseases and to enhance quality of life.
In summary, tumor angiogenesis is a critical target for cancer prevention. Natural antiangiogenic molecules are present in numerous dietary sources and represent a wide spectrum of mechanisms that can suppress the growth of microscopic tumors. The control of blood vessel growth through dietary antiangiogenesis promises to redefine cancer as a disease that can be suppressed throughout an individual’s lifetime, from infancy through adulthood.
The author would like to thank Erwin Kruger, Justin Leahey, and Joy Li for their assistance in research, data compilation, codification, and analysis.