A total of 188 international experts from 32 coun- tries met at the University of St. Gallen, Switzer- land for a 3-day conference to discuss the recent developments in the field of cancer prevention.
The meeting was organized and co-sponsored by St. Gallen Oncology Conferences, the European School of Oncology (Milan, Italy), the Interna- tional Society of Cancer Prevention (New York, NY, USA), the European Cancer Prevention Organisation (Brussels, Belgium), and this year for the first time by the European Society of Med- ical Oncology (Lugano, Switzerland). The local organizers were Prof. Hans-Jörg Senn, MD, and Prof. Ursula Kapp, MD, both from the Center for Tumor Detection, Treatment and Prevention (ZeTuP) in St. Gallen, Switzerland.
In a rather provocative opening lecture, can- cer survivor Clifton Leaf, editor of Fortune Mag- azine, New York, USA tried to answer the ques- tion “Why we are in danger of losing the war on cancer?”, which was meant to encourage scien- tists, clinicians, and the general public to spend more work and money on cancer prevention. He made it very clear that because of demographic development, global cancer rates could increase by 50% to 15 million a year by 2020. The age-ad- justed cancer death rate per 100,000 population has remained constant since 1950, with about 200 cases per year. In contrast, the age-adjusted death rate from heart disease decreased signifi- cantly due to efficient means of prevention. Clif- ton Leaf tried to give a wake-up call encouraging greater effort on cancer prevention because of the terrifying loss of human potential, especially in view of the rapidly increasing economic cost of cancer treatment, which in the future might possibly paralyze any public health system.
Peter Greenwald (NCI, Bethesda, MD, USA) responded with a more optimistic lecture on the
“Progress in Cancer Prevention” and discussed how public guidance (smoke-free environment, diet), chemopreventive drugs (e.g., statins, finas- teride), bioactive food, and screening programs could be successfully applied in the preven- tion of lung, breast, colon, and prostate cancer.
Other epidemiologists and scientists working in basic research gave insights in strategies, how biological knowledge can elucidate potential new targets for cancer prevention or for the definition of certain risk groups.
Tak W. Mak (Toronto, Canada) emphasized the emerging concept in cancer research that can- cer therapeutics should be targeting cell survival genes that prevent cancer cells from dying and discussed research projects that have dissected these signaling pathways, activating cell survival via NFkappaB or PI3K activation, or via activa- tion of anti-apoptotic genes. Helmut Bartsch (Heidelberg, Germany) investigated polymor- phisms in metabolic and repair genes in a lung cancer case–control study and concluded that specific metabolic and DNA repair gene variants can affect cancer risk and therapy outcome. But large population-based studies have to follow.
Michael Pollak (Montreal, Canada) gave an up- date on insulin-like growth factor and insulin- related signaling, which initiates signal transduc- tion via PI3K or MAPK, key components in the control of cell survival and proliferation. He de- scribed how IGF-serum levels correlate with the risk of epithelial cancer, particularly advanced prostate and postmenopausal breast cancer, es- pecially if the serum level is elevated at an early age. He also discussed the question of whether
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IGF-I inhibiting drugs such as metformin could be candidates for cancer prevention.
Chemoprevention is an important issue in cancer prevention. In hormone-responsive tu- mors such as prostate and breast cancer, block- ade of the hormonal stimulus is used as a target for preventive intervention. Peter Greenwald (Bethesda, MD, USA) and Hans-Peter Schmid (St. Gallen, Switzerland) discussed data from the prostate cancer prevention trial (PCPT), which investigates the effect of the testosterone inhibi- tor finasteride on prevention of prostate cancer.
Treatment with finasteride in this study reduces the incidence of prostate cancer by 25%, but the cancers occurring in the treatment group more commonly present with a higher Gleason score of 7–10 and might be more aggressive. Therefore finasteride is not yet ready for clinical use as a chemopreventive agent against prostate cancer outside of clinical trials.
The role of estrogen in the development of breast cancer was extensively discussed by An- thony Howell (Manchester, UK), Irma and José Russo (Philadelphia, PA, USA), Per Hall (Stock- holm, Sweden), and Trevor Powles (London, UK). As Anthony Howell pointed out, estrogen withdrawal for prevention of breast cancer, in- ducing early menopause, results in a significant reduction of breast cancer incidence. Trevor Powles gave a nice overview of current trials in- vestigating the use of selective estrogen receptor modulators (SERMS) for breast cancer preven- tion. It is well known that tamoxifen reduces the early incidence of breast cancer by about 40%.
It also reduces bone loss and serum cholesterol, but on the other hand increases the risk of en- dometrial cancer and thromboembolism. The benefit of tamoxifen intake is limited to high-risk premenopausal and younger postmenopausal women after hysterectomy. A new generation of SERMs – e.g., raloxifene, arzoxifene and la- sofoxifene – has been developed, which have been shown to be more potent than tamoxifen and might have fewer side effects. It is possible to substantially reduce the incidence of breast can- cer in healthy women using SERMS. Numerous trials are under way.
Promising data were shown by Vikas Khurana, Shreveport, LA, USA, who gave a talk on a ret- rospective case–control study, showing a cor-
relation between the incidence of pancreatic cancer and intake of statins. Statins are known to suppress cell growth and cause inhibition of carcinogen-induced tumors in animal models.
In presenting this study, he noted that the use of statins was associated with a 63% risk reduction for pancreatic cancer after controlling for age, gender, smoking, alcohol use, and diabetes. A correlation with the duration of statin use could also be shown. However, prospective studies are still missing.
The use of celecoxib for prevention of colon cancer was discussed by Monica Bertagnolli (Boston, MA, USA). It is well known that treat- ment of familial adenomatous polyposis (FAP) by the COX-2 inhibitor celecoxib leads to a sig- nificant reduction in polyp number and polyp burden. Thus chemoprevention trials with COX- 2 inhibitors were initiated in 1999 for prevention of colorectal adenomas, Barrett’s esophagus, and bladder cancer. Since unfortunately an elevated cardiovascular toxicity was detected with the use of COX-2 inhibitors in these chemopreven- tion trials, the human trial on celecoxib was suspended. This is a major drawback for the investigation of useful preventive drugs such as COX-2 inhibitors. Work on these agents should be continued, since many questions remain un- answered. We must identify subsets of patients for whom the risk-benefit-balance could be fa- vorable. In addition, the question remains of whether successful chemoprevention requires long, continuous drug administration.
In contrast, prevention of cervical cancer has made better progress. Brad Monk (Orange, CA, USA) presented promising results of vaccination strategies against human papilloma virus (HPV).
In a phase III trial, a HPV 16/18 vaccine could prevent more than 70% of cervical cancers. This vaccine will be available for routine clinical use in late 2006.
Another important topic of the conference was the role of lifestyle and food components for cancer prevention. Cheryl Rock (San Diego, CA, USA) discussed primary dietary prevention of colon cancer. Four intervention studies have tested the effect of fiber supplementation. Unfor- tunately no effect was shown on adenoma recur- rence. A specific link between fiber intake and colon cancer risk could not be established. But
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there might be indirect benefits of dietary fiber relevant to colon cancer, because dietary fiber is a key feature of a diet low in energy density. For prostate cancer, the impact of lycopenes, which can be found in tomatoes, as well as phytoes- trogens, selenium, and vitamin E was discussed by Peter Greenwald (Bethesda, MD, USA) and Hans-Peter Schmid (St. Gallen, Switzerland). Vi- tamin E and selenium are presently being inves- tigated in the SELECT trial; especially selenium might be a promising food supplement for pre- vention of prostate cancer in the near future.
Clarissa Gerhäuser (DKFZ, Heidelberg, Ger- many) and collaborators presented their work on food components with cancer preventive poten- tial. One of those components is xanthohumol, which is a flavonoid derived from hop and was identified as an interesting chemopreventive agent with antiestrogenic activity and as an an- tiangiogenic agent. Also, cloudy apple juice con- tains polyphenols that could be shown to prevent intestinal adenoma formation in the APC Min/+
mouse model for colon cancer prevention. Wil- liam Grant (San Francisco, CA, USA) talked about the role of vitamin D in cancer prevention.
He promoted vitamin D as a food supplement that has been shown to increase cell differentia- tion, suppress genes responsible for enhancing cellular proliferation, and possibly of reducing metastasis.
As a future perspective, Anna Barker (Bethesda, MD, USA) gave a keynote lecture on the potential use of nanotechnology in can- cer prevention. In nanotechnology molecules smaller than 50 nanometers, which can easily en- ter cells and react with molecules inside the cell,
could potentially be used for repair of DNA, kill- ing of cancer cells and many other applications.
Nanotechnology is a future technology. We do not yet know how long it takes until this would constitute a safe technology for everyday clini- cal use, and it remains unclear which potentially dangerous side effects might be involved in this technology. However, it may very well revolu- tionize medical practice, also in cancer preven- tion.
Finally Peter Boyle (IARC, Lyon, France) in his closing lecture, presented a summarizing overview of the current issues in cancer preven- tion. He pointed out the crucial problems with the increasing worldwide cancer burden and cost because of the demographic development. He concluded that there is an important role for che- moprevention in the future and a great need to develop nontoxic compounds. In addition, bet- ter biological (surrogate) markers and statistical methodologies are required. “We no longer wait for cardiovascular disease to develop before in- tervening.” It should be the same for malignant disease. Thus effort and money must be spent on the development of equivalent safe and effective drugs, and informative biomarkers for the prog- ress of cancer prevention. This would be a con- structive investment in the future.
The organizers and the international scientific committee of this bi-annual meeting on cancer prevention are carefully monitoring the prog- ress in this field over the next 2 years and plan to invite dedicated scientists, epidemiologists, and clinicians currently interested in primary and secondary cancer prevention to the next confer- ence to be held in St. Gallen in early 2008.
