Northeastern Ontario Cancer Therapeutics Research Initiative (CTRI)

Transcription

1 Northeastern Ontario Cancer Therapeutics Research Initiative (CTRI) Contents: 1. Project Summary 2. Operating Structure 3. Executive Summary 4. Financial supports requested 1. Project summary The land in northern Ontario contains a vast amount of boreal forest and a rich variety of minerals, which provide a tremendous opportunity for economic development with these two natural resources. However, the natural resource-based industry is very volatile, as it is heavily dependent upon the demands from other parts of the world. Thus, there is an urgent need for diversifying the basis of our economy in northern Ontario. Medically oriented research has been steadily developed in northeastern Ontario during the past decade and a half, and has been playing an important role in connecting education, training of highly qualified personnel, job creation and health care. In particular, the establishment of the Tumor Biology Group at the Northeastern Ontario Regional Cancer Centre (currently, Regional Cancer Program [RCP] of the Sudbury Regional Hospital [HRSRH]) was truly a turning point for the establishment of our Cancer Centre/Sudbury Regional Hospital into the hub of cutting edge medical research in northeastern Ontario. Since its establishment in 1996, members of the Tumor Biology Group have published numerous scientific papers, many in top scientific journals such as Nature Structural and Molecular Biology, Journal of Clinical Oncology, and Proceedings National Academy of Sciences (USA); brought in nearly 20 million dollars of research funds; trained over 70 highly qualified personnel; and created over 30 full time jobs. During this period, Laurentian University (LU) has also transformed itself into a more research-oriented university. Another important development was the establishment of the Northern Ontario School of Medicine (NOSM) in These positive developments now provide a truly important momentum for our medically oriented research taking off in northeastern Ontario and potentially becoming an economic engine. Canada spends a significant portion of its GDP on purchasing anticancer therapeutic agents, mostly from abroad. Therefore, developing and producing effective anticancer drugs by Canadians will bring in tremendous financial and social benefits to our country. If a concerted effort of anticancer drug research and development takes place in northeastern Ontario, this will give us enormous opportunities for better education, training, and development of businesses based on knowledge and cutting-edge technologies. To facilitate the development of cancer drug research, Dr. Hoyun Lee organized a Cancer Drug Discovery consortium in 2008, which was comprised of the following members: three scientists and one oncologist from RCP/HRSRH, two professors from LU, one professor from NOSM, one scientist from the Great Lakes Forestry Centre in Sault Ste. Marie, one professor from the University of Western Ontario in London, one scientist from Pfizer Pharmaceuticals, and one professor from the University of Ottawa. To exchange ideas and expertise, and to further facilitate cancer drug discovery, the consortium held a day-long symposium at RCP/HRSRH in CTRI Executive Summary (Feb 2010) 1

2 May Several non-member experts in the cancer drug research field were also invited to the symposium. Owing to the great success of our inaugural annual Cancer Drug Discovery (CDD) symposium, the participants decided to transform the initial consortium into a more functional initiative; thus, we established the Northeastern Ontario Cancer Therapeutics Research Initiative (CTRI) in September The long-term goal of the CTRI is to establish a world class pharmaceutical research hub in northern Ontario. We envision that over 120 new scientists and students will devote their energy and time in pharmaceutical research by the year 2025 under the umbrella of the CTRI. By this time, the direct annual research budget of the CTRI, funded by a variety of agencies, would be over $10 million. In addition, the research activities by CTRI members would create several spinoff biotechnology or pharmaceutical companies in northern Ontario. Thus, the total output by CTRI and associated activities would reach at least $20 million per year by the year Our short-term goal is to establish an essential infrastructure for CTRI members; networking scientists involved in cancer drug research throughout (northern) Ontario; providing expertise, and natural products and synthetic compounds to CTRI members; maximizing research output by CTRI members; and facilitating the commercial utilization of knowledge/data generated by CTRI members. The ultimate goal of the CTRI is developing very effective anticancer drugs. However, the contribution by the CTRI to the progress of science and economic development of the local community and Canada will be very significant even without developing a blockbuster cancer drug. If the CTRI is able to develop a blockbuster drug, it will certainly create an opportunity of developing a powerful new industry in northern Ontario. To effectively achieve our goals, we will establish Central Services I (CSI) and Central Services II (CSII). The CSI, which is to be stationed at RCP/HRSRH, will provide necessary infrastructure, expertise, synthetic compounds and natural products, modifications and characterization of existing anticancer drugs, and coordinating and facilitating collaborations between members and CSII. The CSII, which is to be housed at the Great Lakes Forestry Centre in Sault Ste. Marie, will focus on collection, purification, and characterization of natural products. The Office of Development, which is to be located at RCP/HRSRH, will be the central nerve system coordinating communications between members and the two Central Services stations. The Office of Development will also coordinate disbursement and development of data and products generated by CTRI members, and explore commercialization of promising pharmaceutical agents developed by CTRI members. The CSII, which will be headed by Dr. Mamdouh Abou-Zaid, has accumulated 2,000 natural products. Most of these natural products were extracted from plants and trees growing in northern Canada. It should be noted that American/Canadian yew trees, which are the source of Taxol, a widely prescribed anticancer drug, are part of the northern Ontario boreal forest. Dr. Abou-Zaid obtained a patent for an improved Taxol extraction method from Canadian yew trees. Dr. John T. Arnason, a CTRI member and Full Professor at the University of Ottawa, has also accumulated 1,500 natural products collected from rainforest regions throughout the world, including the Amazon basin in South America, Africa, and Indonesia. Dr. Hoyun Lee (RCP/HRSRH), the Founding Chair of the CTRI, has already screened 36,000 natural and synthetic products in collaboration with Dr. Eric Brown of McMaster University using his high throughput screening facility. The Lee group is currently characterizing ~1,000 lead compounds identified by the high throughput screening to develop effective and safe anticancer drugs. The CTRI Executive Summary (Feb 2010) 2

3 CSI will carry out initial screening of the 3,500 natural products collected by Drs. Abou-Zaid and Arnason. If promising leads are identified, participating CTRI members will further study the natural products to develop them into effective cancer therapeutics. In addition to this group effort, each member will be strongly encouraged to carry on their own cancer drug research programs with their own ideas. This is important because innovation is ultimately the most important winning formula for cancer drug discovery. We consider that the most important strengths of our CTRI initiative are innovation, flexibility, mobility, and rapid adaptability of individual members and the very flexible two Central Services systems that provide infrastructure, technology and expertise to each CTRI member. Along with the unique collection of natural products described above, this rapid adaptability of individual CTRI members will provide tremendous advantage over other cancer drug researchers, even large pharmaceutical companies. Currently, the CTRI Core members include Drs. Hoyun Lee (cancer biologist, affiliated with RCP/HRSRH, NOSM, LU, and UO), Robert Lafrenie (cancer biologist, affiliated with RCP/HRSRH, LU, and NOSM), Pablo Cano (medical oncologist, RCP/HRSRH), Mamdouh Abou-Zaid (medicinal chemist/phytochemist, affiliated with Great Lakes Forestry Centre in Sault Ste. Marie), Ed Lui (biologist/herbalist, affiliated with UWO and Algoma University), Gerardo Ulibarri (medicinal chemist, LU), and John T. Arnason (medical botanist, UO). The CTRI Collaborators members include Drs. Leslie Sutherland (cancer biologist, RCP/HRSRH, LU, NOSM, and UO), Sabine Montaut (medicinal chemist/herbalist, LU), and Stephen Fields (biologist/pharmacologist, Pfizer Pharmaceuticals). We believe that the CTRI has all the ingredients necessary to be successful enthusiastic and innovative scientists with complementary expertise; many promising compounds already in possession (which is extremely important and exciting); proven capability of collection, isolation, purification, screening, modifications, and characterization of natural and synthetic products with potential anticancer properties; and strong and enthusiastic support by participating institutions and local communities (particularly, the City of Sault Ste. Marie and the City of Greater Sudbury). We do not have any doubt that the CTRI will greatly contribute to high levels of training, education, research, drug development, and high-value job creation for local communities and Ontario as well as for our country. In addition, this initiative will certainly provide an excellent reputation, pride, and significant financial benefits to northestern Ontario. This is truly a cannot miss momentum for northern Ontario! The operating structure of the CTRI is discussed in the following pages. CTRI Executive Summary (Feb 2010) 3

4 2. Operating Structure CTRI Executive Summary (Feb 2010) 4

5 The CTRI will be established in two distinct steps, an Early Stage (Figure 2) and a Mature Stage (Figures 3). During the Early Stage, the CTRI will focus on the following three aspects: (i) research and development, (ii) training and education of highly qualified personnel (HQP), and (iii) commercialization of services and products. The CTRI will not be heavily involved in commercialization activity within the first three to four years of its establishment. However, the CTRI will be actively pursuing research service contracts with commercial companies. As our Chemistry Laboratory gains a reputation, the CTRI will also be able to provide medicinal chemistry services to scientists in academics and industry. The fourth and fifth years will be a transitional period that the CTRI is involved in more commercialization activities. As the portion of the commercialization activities increase, the CTRI commercialization arm will gradually evolve into independent for-profit companies while the CTRI remains as a research arm. As shown in Figure 3, the CTRI will eventually function like a research arm of many commercial companies created by (and associated with) the CTRI. Under this proposed organization, the data generated by the CTRI and its members will be channeled into the commercial companies associated with CTRI. This data may help the companies to establish and execute their strategic plans. In return, these companies will provide the CTRI with information obtained from the front line of health care and services. This will help the CTRI in adopting and establishing new research directions in real time. Since these small start-up companies associated with the CTRI do not need to carry on their own research (i.e., the CTRI functions as their research arm), they will be able to establish profitable companies rather quickly. Thus, this operating system will give the CTRI and associated companies very powerful synergistic effects. CTRI Executive Summary (Feb 2010) 5

6 3. Executive summary The most important and exciting possibility is that a new industry cluster may be created in northern Ontario as a result of the CTRI. Indeed, this new initiative by scientists with an entrepreneurial spirit has great potential of creating a new economic engine for local communities as well as for Canada. Some detailed points are shown below: Ten scientists from six different institutions participate in the Northeastern Ontario Cancer Therapeutics Research Initiative (CTRI) as principal investigators (PIs). The ten PIs are from the following institutions (see Figure 1): four PIs are from the Northeastern Ontario Regional Cancer Centre of the Sudbury Regional Hospital/the Northern Ontario School of Medicine; two PIs from Laurentian University; one from the Great Lakes Forestry Centre in Sault Ste. Marie; one from the University of Ottawa in Ottawa; one from the University of Western Ontario in London; and one from Pfizer Pharmaceuticals Inc. in Toronto. The ten CTRI members have a diverse scientific background, spanning from molecular and cancer biology to pharmacology and medicinal chemistry. Thus, this group can be very powerful if they can put their expertise and energy together under one consolidated objective. The resultant synergy can be many times more powerful than the sum of output by the ten individual PIs. The laboratory led by Dr. Hoyun Lee has already screened 36,000 drug-like compounds to identify potential anticancer drugs. They have identified 1,000 promising leads, which are currently being further examined for their anticancer properties. Dr. Mamdouh Abou-Zaid, a phytochemist at the Great Lakes Forestry Centre in Sault Ste. Marie, has collected 2,000 natural products, mostly from northern Canada. Some of these products are expected to contain powerful anticancer property. Dr. Abou-Zaid also obtained a patent for the effective purification method of Taxane (i.e., Taxol ) from Canadian yew trees, which widely grow throughout northern Ontario. Taxol is one of the most widely prescribed anticancer agents. Dr. Robert Lafrenie found that natural products from cats claw and flax seeds contain components with effective radiosensitization and anticancer properties, respectively. Dr. Lee group found that chloroquine, an inexpensive and safe anti-malarial and antirheumatoid agent, can preferentially kill cancer cells 100 times more effectively than normal cells. Dr. John T. Arnason, a medicinal herbalist and Professor at the University of Ottawa, has accumulated 1,500 natural products collected from rainforests throughout the world, including the Amazon basin in South America, Africa, and Indonesia. These natural CTRI Executive Summary (Feb 2010) 6

7 products are known to have healing effects for a variety of human diseases by local people. Thus, this collection is particularly promising. The CTRI will provide excellent training opportunities for highly qualified personnel, including post-md, post-phd, retraining of healthcare professionals such as pharmacists, pharmacologists, and oncologists, and graduate students. The CTRI-initiated training opportunity is unique, as the trainees will be exposed to both academic and industrial environments. The CTRI will directly create at least 25 new positions within five years, and 120 positions by the year A similar number of new jobs will also be created indirectly through commercial companies created by (and associated with) CTRI members. If CTRI develops a blockbuster drug, the number of jobs created by the CTRI can easily exceed 1,000 by the year Thus, there is really an excellent possibility of creating a new economic engine in northern Ontario. Considering the excellent and unique human and natural resources that we have, there is excellent potential of developing effective blockbuster anticancer drugs by the CTRI and its members. A dramatic increase in scientific output. The scientific output (publications, presentations, and obtaining patents) by CTRI members will double within five years, which will raise our reputation world-wide. As a result of numerous collaborations and other synergistic effects, the scientific output may increase ten-fold by the year Importantly, the CTRI has obtained strong support from participating institutions, and local communities including the City of Sault Ste. Marie and the City of Greater Sudbury. 4. Financial supports requested by the CTRI The following table shows summary of financial supports being requested by the CTRI for setting up infrastructure and operation of the initiative for the first five years. It is anticipated that the CTRI will not need further financial aid from the same funding sources after the initial funding for five years. Funders Equipment (Chem Lab) CSI CSII Training & Operation Office of Develop Total FedNor 1,315, , , ,125 $2,719,359 NOHFC 1,315, , , ,125 $2,719,359 City of Sudbury 0 900, , ,250 $1,436,700 City of Sault Ste Marie , ,550 0 $668,550 Total fund requested $2,631,468 $1,425,000 $510,000 $2,265,000 $712,500 $7,543,968 Total matching fund $7,543,968 Total budget $15,087,936 CTRI Executive Summary (Feb 2010) 7