Asia-wide collaborative clinical research on Prostate Cancer

Recent Progress on Nanobio-target Therapy at ICONT and Initiation of An Asia-wide Translational Research .

Hiromi KUMON
Professor and Chairman, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Okayama University is conducting a fully developed national project to form the Innovation Center Okayama for Nanobio-targeted Therapy (ICONT) with resources from both the government and collaborating companies. To date, its research and development accomplishments are superb, especially in the gene therapy field. Okayama University, where promising scientific seeds are being sewn and clinical trials staged, demonstrates leading performances in Japanese gene therapy; its biotech startup company was created to promote drug development.

Furthermore, in this year’s competition for government Special Coordination Funds for Promoting Science and Technology, Okayama University’s proposal of “An Asia-wide translational research on high-risk group detection based on ms-SNP and IL-12 immunogene therapy for prostate cancer” has been adopted to consolidate translational research infrastructure in Asia with the cooperation of top institutes in China, Korea and Singapore.

The current accelerating progress in creating a globally recognizable gene therapy research center at Okayama University is reported, and the prospects of its mutually beneficial relationship with Asia are presented.

Beneficial effects of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer.

Yasutomo NASU
Associate Professor, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Interleukin-12 is a potent cytokine which activates an anti-tumor immunity. We initiated IL-12 gene therapy against prostate cancer using adenovirus vector from May 13, 2008 after an official approval of the government. In this project, protocols and technique will be introduced to the collaborating countries. Thorough the promotion of clinical studies we will establish the translational research network in advanced clinical application fields including gene therapy.

We have analyzed genotypes of about 300 SNPs in cancer-related genes on 450 controls and 1,300 patients with a variety of cancers. We found that 48 missense SNPs of 43 genes are associated with incidence of at least one of 8 major cancers in Japan, including lung, head & neck, esophageal, colorectal, gastric, pancreatic, breast and prostate cancers. Associations of 39 of these 48 SNPs with any cancer are novel findings. Of 101 significant single associations, 59 were very significant in 99% confidence interval and in permutation test. We then addressed the overlap of the SNP genotypes at risk in each individual. The net numbers of overlapping SNPs were much higher in cases than in controls for all cancer types. Thus, we demonstrate that about 0.5 to 10% of healthy subjects can be identified as the highest-risk group for each major cancer in Japan. Since Asians share the common genetic background, our strategies can be expanded on whole Asia. Especially, we are focusing into prostate cancer, which is rapidly increasing in most Asian countries and discuss the concrete perspectives for the collaboration.

科学技術振興調整費による、アジアにおける共同研究推進のためのプログラム（日本） （A program for promoting Asian collaborative research by Special Coordination Funds for Promoting Science and Technology in Japan）

独立行政法人　科学技術振興機構　科学技術振興調整費プログラム主管
西垣　隆

日本における科学技術政策は、その基本方針が内閣総理大臣を議長とする総合科学技術会議（Council for Science and Technology Policy: CSTP）において討議、立案され、閣議での決定、そして予算措置など政策実施に向けて必要な過程を経て、それぞれの関係省庁により実施されます。

こうした科学技術政策の基本方針の実施において、政策誘導に向け、そのきっかけを作るためのファンドとして科学技術振興調整費が使われています。科学技術振興調整費は、文部科学省　科学技術・学術政策局　科学技術・学術戦略官付（推進調整担当）がその運用（公募、審査、資金配分、評価等）を行っています。また、独立行政法人　科学技術振興機構に事務の一部が委託されています。

科学技術振興調整費は、総合科学技術会議の方針に沿って科学技術の振興に必要な重要事項の総合推進調整をおこなうための経費であり、以下の施策であって、各府省の施策の先鞭となるもの、各府省ごとの施策では対応できていない境界的なもの、複数機関の協力により相乗効果が期待されるもの、機動的に取り組むべきもの等で、政策誘導効果が高いものに活用されます。

1. 1） 優れた成果の創出・活用のための科学技術システム改革
2. 2） 将来性の見込まれる分野・領域への戦略的対応等
3. 3） 科学技術活動の国際化の推進

科学技術振興調整費にはいくつかのプログラムがありますが、この３）に挙げられる国際化の推進に向けたプログラムとして、2006年から実施されていますアジア科学技術協力の推進プログラムがあります。2008年度からアジアに加えて、アフリカ地域も対象地域として加わりましたが、本プログラムは、アジア･アフリカ諸国における先端技術を有する国々との科学技術協力を強化するとともに、日本の研究機関とこれら諸国の優れた研究機関との相互補完的な（イコールパートナーシップの精神にもとづく）国際共同研究の実施等を支援するものです。

公募に際して毎年数多くの提案が寄せられ、競走率の高いプログラムとなっていますが、今年、岡山大学 公文裕己教授が代表となって提案された、中国、韓国、シンガポールの研究機関との間で共同臨床研究を推進しようとする「アジア人の癌体質と遺伝子治療共同臨床研究」プロジェクト（An Asia-wide Translational Research on High-risk Group Detection Based on Ms-SNP & IL-12 Immunogene Therapy for Prostate Cancer.）が採択プロジェクトの一つとなりました。本プロジェクトの実施期間は3年間です。

このプロジェクトは癌に対する遺伝子治療をはじめとする先端医療技術の開発、そして医師主導の探索臨床研究におけるアジアネットワークの構築を目指すものです。本共同研究に参加される、北京大学（那彦群　教授、中国泌尿器学会理事長）、北京腫瘍病院（李鳴　教授）、浙江大学（謝立平　教授）等の中国研究機関は前立腺癌の治療に向けた臨床研究、そして遺伝子治療の実施において実績を有しており、日本おける癌体質研究また遺伝子治療研究において実績を有する岡山大学他との共同研究を行うことにより、その成果に大きな期待が持たれます。

Current Status of Prostate Cancer in China

Ming LI
Director, Professor, Peking University School of Oncology, Beijing Cancer Hospital & Institute

Prostate cancer incidence has been rapidly increased in China. Data from most of the cities and area in China in year 1988-2002 showed a sharp increase trend of incidence of prostate cancer. In year 1988-1992 PC incidence in China was 1.96/10,000, in year 1993-1997 was 3.09/10,000, and in year 1998-2002 was 4.36/10,000. Data from several single institutes since 2002 up to now showed also remarkable increased trend.

More recently, studies demonstrated that there was about 1/4 prostate cancer with PSA less than 4ng/ml. Some of the urologists in the USA and European countries suggest to lower the PSA value to 2.5ng/ml, so that to increase diagnostic rate and to find more earlier stage prostate cancer. Is this lower PSA cutoff point applicable to Chinese men? Data showed that the prostate cancer detection rates in the tPSA ranges of ＜4ng/ml, 4-10ng/ml were 3.1%, 11.6% respectively. To lower PSA cutoff point to ＜4ng/ml may not be applicable to Chinese men except positive DRE.

Since PSA was introduced In China in early 1990s, more and more early stage prostate cancer patients have been diagnosed. There are currently about 20-30% localized prostate cancer patients who received radical prostatectomy, which compared to ＜10 % patients who received radical prostatectomy in 1980s. Even though more and more early stage PC was detected, there are still more than half late stage PC patients at diagnosis. The major reason is that it’s still impossible to do PSA screening for the population in China. We do PSA test only for the patients who are older than 50 years and see doctors for LUTS or other urinary symptoms.

Treatment selections for PC are extremely various in different parts of China. More accurate pre-treatment staging and grading were done and more curable techniques were selected in big cities, while more operative castration was used in the rural area. In 2006 Chinese Urological Association (CUA) organized specialists from all over the China to make guideline for prostate cancer and published the “China guideline for prostate cancer” in 2007. The aim of the guideline is to improve the diagnosis and treatment for PC and to unify the opinion of urologists in all over of China.