A Major Boost for Cancer Drug Discovery

May 13, 2011

Dean Robert Alpern: 333 Cedar Street

333 Cedar Street is a monthly letter from Dean Robert J. Alpern, MD, Ensign Professor of Medicine, on topics of interest to the Yale School of Medicine community. Write to Dean Alpern at 333cedar@yale.edu.

At a time when collaborations between academia and industry are on the rise, agreements like the one with Gilead Sciences offer a promising route to better therapies for cancer.

To The School of Medicine Community,

On March 30, the School of Medicine and Gilead Sciences, Inc., announced a research collaboration that stands to have a transformative effect upon Yale’s contributions to the field of cancer biology. Gilead, a biopharmaceutical company headquartered in Foster City, Calif., has committed up to $100 million over the next 10 years to set up a multidisciplinary research program focused on advancing our understanding of the fundamental mechanisms of cancer, thus leading the way toward the discovery of novel cancer therapies. Under the agreement, Gilead will provide $40 million to support research at the School of Medicine over the first four years of the project—and a total of up to $100 million if the collaboration is extended for the full 10 years. This would amount to the largest corporate commitment to Yale in the university’s history.

The Gilead announcement comes at a time of unprecedented interest in applying the knowledge gleaned in academic labs toward the development of new treatments for cancer. More than ever, detailed understanding of drug targets is coming from research in universities, making them a valuable partner for industry. Public opinion is also supportive; overwhelmingly, Americans think the institutions conducting medical and health research, such as the government, universities, and private industry, should work together to develop new treatments and cures.

Top scientists to lead project

Our project with Gilead is exciting for a number of reasons. It leverages unique and tremendous strengths in basic and clinical science at Yale and opens up a real possibility that more effective and longer-lasting cancer therapies, with fewer side effects, will be available to patients in the foreseeable future. Yale has made major investments over the past decade in cancer research and related technologies, including genomics, proteomics, cell imaging, X-ray crystallography, and small molecule screening. The recently announced Yale Cancer Biology Institute, led by Joseph Schlessinger, PhD, on Yale’s West Campus, will be a central component of our new collaboration with Gilead. The West Campus is also home to the Yale Center for Genome Analysis, which is overseen by Richard Lifton, MD, PhD, and offers high-throughput DNA sequencing to identify disease-causing mutations in cancer cells. These valuable resources for cancer research complement formidable and growing strength in cancer care and clinical trial development at the Yale Cancer Center and Smilow Cancer Hospital under the direction of Thomas Lynch Jr., MD, a third leader of the collaboration. Tom Lynch has extensive experience with clinical trials of targeted cancer therapies and is one of the country’s top experts in personalized medicine and targeted therapies for lung cancer.

Overall, the Gilead venture is testament to the enormous promise of cancer research at Yale and the great synergy inherent in the collaboration of the three outstanding scientists mentioned above. The project will be governed by a six-member Joint Steering Committee chaired by Dr. Schlessinger and including Drs. Lifton and Lynch, along with Gilead scientists Howard Jaffe, MD ’82, president and chairman of the board of the Gilead Foundation; William A. Lee, PhD, senior vice president, Research; and Linda Slanec Higgins, PhD, vice president, Biology.

The search for novel drivers

Collectively, these six individuals will oversee a highly focused research effort to define novel driver genes for cancer and identify mechanisms of metastasis and drug resistance. A key component of the collaboration will be the development of new strategies necessary to ensure optimal tissue procurement and accessibility for subsequent research analysis. The genetic material of those samples will be sequenced in the Center for Genome Analysis on West Campus, and the results will be analyzed by Yale scientists with an eye to mapping out the shared mechanisms and functional pathways among tumor types that are related to cell proliferation, inhibition of cell death, metastasis, and drug resistance. The goal of this work is to identify links in the chain that may be interrupted by new cancer drugs.

In the course of the work, we hope this collaboration will expand the frontiers of cancer biology and facilitate the development of new technologies and scientific approaches to cancer. We have every expectation of identifying molecular targets that could potentially lead to new personalized therapies and approaches to overcoming drug resistance with a goal of improving quality of life and long-term survival for patients living with cancer.

Unlike some previous academia-industry collaborations at Yale, in which calls for proposals were issued, the course of this collaboration will be directed by the Joint Steering Committee. It is likely that work done in the initial years will open up new directions and lead to expanded opportunities for faculty across the university, but at the outset the research plan is quite focused and the committee will engage faculty opportunistically and strategically.

Gilead's culture is a good fit

I am delighted with the choice of Gilead as our collaborator in this venture. Gilead brings many attributes to the enterprise that inspire confidence and assure us that we can work together effectively. From the start, Gilead has demonstrated its understanding of the university’s culture and working environment. As with any collaboration, it is of paramount importance that the work of Yale scientists be driven academically. This requires that Yale be fully in control of decision-making on the questions to be investigated, the training activities of our postdoctoral fellows and graduate students, and the publication of findings. It must be possible to publish the results of this work, as is the case with all the research done here. Gilead will have the first option to license intellectual property resulting from the collaboration.

Another reason this is a good match is the culture at Gilead, which is dedicated to discovering drugs to address unmet medical needs and to making sure those medications reach patients, regardless of their economic status. Gilead has worked with more than a dozen manufacturers in India, Africa, and the Caribbean to make and distribute generic versions of its HIV medications at lower cost in nearly 100 countries and regions around the world. The company also shares some history with Yale. Howard Jaffe earned his medical degree at Yale. Gilead’s CEO, John C. Martin, PhD, was at Bristol-Myers Squibb in Wallingford, Conn., in the 1980s and ’90s and was closely involved in the collaboration with Yale pharmacologist William H. Prusoff, MD, that led to the introduction of Zerit, one of the first effective AIDS medications and part of the AIDS cocktail that began to alter the deadly course of the HIV epidemic. Dr. Martin and Dr. Prusoff, who sadly passed away on April 3, were co-authors on a 1989 paper that showed Zerit to be a highly potent and selective anti-HIV agent. In 2003, Gilead acquired Triangle Pharmaceuticals, founded by a YSM alumnus, the late David Barry, MD ’69, HS ’72, who was a co-developer of the first AIDS drug, AZT. Last year Gilead acquired another company with Yale ties, CGI Pharmaceuticals of Branford, Conn., whose founders include former Yale faculty members Ira Mellman, PhD, and Mark Velleca, MD, PhD.

As federal deficits have caused limited growth in the NIH budget, Yale must look to other funding sources to continue to expand its research programs. Our collaboration with Gilead is one of a number of drug discovery projects under way and may be a catalyst for similar collaborations in other disease areas. We have been approached by a host of pharmaceutical and biotechnology companies, and it is possible that this work with Gilead will serve as a model and inspiration for future agreements with outside entities that want to pursue important scientific questions with Yale School of Medicine faculty.

Sincerely,

Robert J. Alpern, MD

Dean and Ensign Professor of Medicine