Work cited will revolutionize cancer therapy and impact a potential $700 million global stem cell market.

The 2009 Lasker Awards, which will be announced today, have far reaching implications for the biotechnology and pharmaceutical industries, as companies seek to expand their research and development to fulfill the promise of stem cells. Collaborations between academia and industry will accelerate, particularly in adult stem cell investigation.

“The 2009 Lasker Awards underscore the ways in which our commitment to medical research opens up new areas of inquiry and enables science-based decision making to improve the public’s health,” Maria Freire, Ph. D., President of the Lasker Foundation, told Genetic Engineering and Biotechnology News (GEN). “All six Laureates have played crucial roles in finding solutions to a host of vexing health problems. Lives everywhere may be saved and improved because of their bold innovations in public health, cell differentiation, and cancer treatments.”

Two scientists who made key advances in nuclear reprogramming and stem cell research and three investigators responsible for revolutionizing the treatment of leukemia have won this year’s Lasker Awards.

The Albert Lasker Basic Medical Research Award will be presented to Sir John Gurdon, D.Phil., D.Sc., FRS, Emeritus Professor and Group Leader, Gurdon Institute of Cancer & Developmental Biology, University of Cambridge, and Shinya Yamanaka, M.D., Ph.D., Institute for Integrated Cell-Material Sciences, Kyoto University, for discoveries into the process that instructs specialized adult cells to form stem cells. Click here for a video interview with Drs. Gurdon and Yamanaka.

The 2009 Lasker-DeBakey Clinical Medical Research Award will be given to Brian J. Druker, M.D., Professor of Medicine and Director of the Leukemia Center, Oregon Health Sciences University; Nicholas B. Lydon, Ph.D., formerly of Novartis; and Charles L. Sawyers, M.D., Head of the Laboratory in Human Oncology and Pathogenesis, Memorial Sloan-Kettering Cancer Center, for outstanding therapeutic research on chronic myeloid leukemia (CML). Click here for a video interview with Drs. Druker, Lydon, and Sawyers.

“Both the basic research and clinical awards clearly illustrate the potential of translational medicine to transform healthcare by expeditiously moving new discoveries from the lab into the clinic,”said John Sterling, Editor in Chief, GEN.

“The groundbreaking research efforts of Drs. Druker, Lydon, and Sawyers have already paid off in the development and FDA approval of Gleevec as an effective and well-tolerated treatment for chronic myeloid leukemia. Meanwhile, stem cell expertise gained in the basic research laboratory is efficiently heading toward clinical applications in regenerative medicine. The Lasker awards are a validation of nuclear reprogramming and will serve as a real shot in the arm for the emerging stem cell industry.”

Sterling also believes the focus of the Lasker Awards will help improve the difficult financial environment in which cash-strapped biotech companies have been operating for over a year. “Since the awards highlight both a novel approach to cancer therapy and a promising method for generating stem cells that avoids the immunogenicity problem, this encouraging news is likely to attract significant money that’s been sitting on the sidelines for investment in the life science business,” he said.

Indeed, Kalorama Information estimates that there could be a $500 million global market for stem cell therapies by 2013. Sterling thinks the market might even be closer to $700 million based on the broad range of diseases that could be treated with stem cells and due to the rapidly increasing amount of sophisticated stem cell research taking place on a worldwide basis.

Nuclear Reprogramming

Nuclear reprogramming opened new avenues for pursuing a range of aspects of embryonic and adult stem cell research, understanding inscrutable diseases, and exploring personalized cell-replacement therapies.

Beginning in the mid-1950s, Dr. Gurdon showed that most of the body’s cell types retain all of their genetic information as they specialize and that the right conditions can wake up genes that turn idle during development. Dr. Gurdon’s discoveries in frog eggs ignited the entire field of nuclear reprogramming whereby specialized adult cells turn into stem cells that can then differentiate to form many of the body’s tissues. This line of inquiry with mammalian eggs allowed other work to unfold, including the creation by Scottish scientists of Dolly the sheep in 1997 as the first clone made from the nucleus of a fully specialized mammalian adult cell.

With Dr. Gurdon’s findings in mind but without the need for eggs, Dr. Yamanaka, who is also a Senior Investigator at the Gladstone Institute of Cardiovascular Disease, reported in 2006 the reprogramming of fully differentiated mouse skin cells into stem cells that can specialize into many fetal and adult types of cells. Subsequent research based on the findings of Drs. Gurdon and Yamanaka has the potential to make reprogrammed cells a source of patient-specific cells for use in medicine that will enable the body to regenerate, repair, replace, and restore diseased or damaged cells, tissues, and organs.

“The Lasker Awards confirm the promise of adult stem cells for transplantation-based therapies,” said Mary Ann Liebert, President and CEO of Mary Ann Liebert, Inc., which launched the first peer-reviewed journals in this field: Cloning and Stem Cells, edited by Professor Sir Ian Wilmut, and Stem Cells and Development, edited by Graham Parker, Ph.D.

“Research on adult stem cells has been ongoing for over half a century, but since adult stem cells were thought to be limited to differentiating into different cell types, the excitement has centered around embryonic stem cells. Both embryonic and adult stem cells offer enormous promise for regenerative medicine.”

Professor Wilmut told GEN that he rates the induced pluripotent stem (iPS) cell approach as one of the breakthroughs of this decade and that succeeding generations of scientists may judge iPS as a breakthrough of the new century.

“They are comparatively easy to obtain and combine the main advantages of embryonic stem cells and cells from adults,” he explained. “They can form any tissue and multiply many times in culture, but you also know [their] genotype. Knowing the genotype may be useful in the longer term, because the iPS cells will be an immunological match to the person from whom they were derived.”

The iPS advantage has already been important for a different application, continued Professor Wilmut. “You can use cells from a person who has an inherited disease to study that disease. There are hundreds of different inherited diseases. Projects using iPS cells are already being developed to study diseases as varied as motor neuron disease, some psychiatric diseases, and cancer.”

Dr. Parker, Assistant Professor (Research), Department of Pediatrics, Wayne State University School of Medicine, calls nuclear reprogramming technology a “very exciting development. Some might say [it’s] unbelievable that the introduction of just a few genes can turn a somatic cell pluripotent.”

Dr. Parker, however, also raises a cautionary flag. “The problems and issues that have limited progress of embryonic stem cell research will still apply to induced pluripotent stem cells. We are fantastically ignorant of how the programming to pluripotency occurs,” he explained to GEN. “The efficiency levels are so low as to defy a clear understanding of which genes/proteins at what concentration are truly required. At the moment we are definitely dealing with a phenomenon that we see works and produces something useful, but the details are still squarely in a black box.”

Linda Powers, co-founder and managing director of Toucan Capital, which has 16 stem cell or regenerative medicine companies in its portfolio, thinks the introduction of the nuclear reprogramming technique is quite important for at least two reasons.

“First, iPS has rapidly moved the whole regen medicine field away from embryonic stem cells. This change of focus will extricate the stem cell field from the ethics issues and controversies, which continue to be a restraining factor, even under the new Obama Administration,” she emphasized.

“Second, iPS is turning the whole field’s focus to autologous (personalized) products and treatments. In recent years, the strong prevailing dogma about clinical applications and commercialization in the regen med field has been that products must be allogeneic (nonpersonalized) in order to be commercially and medically practical. We, at Toucan, believe that there are some uses for which allogeneic cells are appropriate: Principally acute situations such as acute MI, where there is no time for an autologous product (at least initially), and situations in which the cells are only being asked to perform limited functions such as trophic support or suppression of inflammation.

“However, we believe strongly that for clinical applications where there is time, and where the cells are being asked to perform actual repair functions, that autologous products and treatments are greatly preferable. In essence, we believe the business model should be made to fit the biology, rather than trying to force the biology to fit a convenient business model. So, we think it is quite important that iPS technology is now turning everyone’s thinking toward autologous products and treatments.”

Cancer Research

Research by Drs. Druker and Lydon, both of whom also are Investigators at the Howard Hughes Medical Institute, led to the development of imatinib (Gleevec). Dr. Sawyers was out front in efforts toward attacking the resistance to Gleevec that arises in some patients. The result: Chronic myeloid leukemia was converted from a fatal cancer to a manageable condition. Gleevec has dramatically redirected approaches to cancer drug discovery and therapy by its mode of action, which targets a specific tyrosine kinase instead of nonspecifically inhibiting cells, which can provoke toxic side effects as standard chemotherapeutic agents do.

The success of Drs. Druker, Lydon, and Sawyers has provided a model that extends well beyond CML. Indeed, many potential drugs for cancer that attack specific troublesome molecules are now in development and dozens have been approved. In addition to radically improving the prognosis for CML, Drs. Druker, Lydon, and Sawyers have provided a new paradigm for cancer therapy.

“Their award is an outstanding example of contributions that have improved the clinical treatment and of collaboration between the public and private sectors,” said Dr. Freire of the Lasker Foundation. “Patients with CML have new hope for the future because of the Laureates’ enormous dedication and inspired clinical research.”

“Gleevec is the most prominent of the first successful agents developed based upon a specific known molecular disease abnormality,” noted Peter C. Johnson, M.D., President and CEO, Scintellix, and Executive Vice President and CBO, Entegrion.

The drug itself is part of a new strategy that will help change the nature of cancer treatment in the future, according to Dr. Johnson. “New systems biology tools are giving us the opportunity to target specific molecular interactions that are responsible for the onset and for the proliferation of cancers,” he pointed out. “Our enhanced understanding of metabolic pathways in cancer will enable us to sharply target cancer-specific abnormalities in rational ways.”

Dr. Johnson predicts that cancer therapy in the future will fall under the umbrella of personalized medicine to the extent that the molecular behavior patterns of specific types of cancers will be known and addressable. “Then, host factors (age, health status) will dictate how these highly specific therapeutics can be administered (locally or systemically, in what doses, and in what combination with other adjunct therapies) to achieve success in the individual setting,” he explained.

Public Service Award

The Mary Woodard Lasker Public Service Award will go to New York City Mayor Michael R. Bloomberg for policy and philanthropic initiatives to reduce tobacco use and promote public health. Mayor Bloomberg was chosen for employing sound science in making policy decisions and advancing public health through enlightened philanthropy. He has been on a crusade to reduce tobacco use and promote healthy eating habits, basically trying to stop disease (e.g., cancer, obesity, and diabetes) before it starts.

The Laser Award Committee points out that Mayor Bloomberg has fueled advances not only through his activities as an elected official but also by backing higher education in public health with broad levels of support and committing $350 million to a global initiative to combat tobacco use.

The Lasker Awards, which carry an honorarium of $250,000 for each category, will be presented at a ceremony on Friday, October 2, at the Pierre Hotel in New York City. For 64 years, The Albert and Mary Lasker Foundation has recognized the contributions of scientists, physicians, and public servants internationally who have made major advances in the understanding, diagnosis, treatment, cure, and prevention of human disease. The three Laskers are considered the most prestigious medical research awards in the U.S. Seventy-six Lasker Laureates have received the Nobel Prize, including 28 in the last two decades.

GEN has created a special blog so that readers can discuss various topics and issues related to the 2009 Lasker Awards. The blog is entitled “Lasker Awards and Applied Biotechnology.” Join the conversation! Go to the BLOGbiotech section and give us your thoughts and opinions at:

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