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DATA MINING
Data Mining researchers unearth new uses for existing medications
By Burke Watson
Stephen Wong has been called a lot of things in his storied career — engineer, developer of the first inkjet printer and the first and largest online trading site. But he has a new name to add to his myriad accomplishments — matchmaker.
Employing computer skills to sort through the vast array of medical data that scientists have compiled digitally over the past decade, Wong and his research team at The Methodist Hospital Research Institute are working to match existing drugs with diseases they weren’t originally created to fight.
The effort, still in its early stages, is drawing widespread attention as it raises the prospect of whittling down some major obstacles, including the staggering cost of bringing a new medication through its long series of clinical trials.
Dr. Stephen Wong holds the John S. Dunn Distinguished Chair in Biomedical Engineering.
Wong’s team uses computer analysis and mathematical models to sort through databases, scientific literature and the FDA database.
“When I come to a new place, I like to start something new,” says Wong, a Ph.D. who along with much of his research group was recruited to Methodist from Harvard University in 2007. He is director of the Center for Bioengineering and Informatics and director of the newly formed H.H. and W.F. Chao Center for Bioinformatics Research and Neurosciences Imaging.
“The cost of making new drugs is ridiculous,” he says. “A study published in 2006 reported that costs vary from $500 million to $2 billion to bring a new drug to market. My philosophy is to look at the drugs we already have and see if we can find a new way to use them.” Also, he said, so many drugs have been developed, it is becoming more difficult for researchers to identify new targets in the body. The U.S. Food and Drug Administration approved only 26 new drugs in 2009, compared with more than 100 a decade earlier. “The traditional way of drug development is running out of steam,” Wong says. “So we have a double whammy here and, basically, we have a drug drought.”
Data Mining
A pioneering spirit
A Hong Kong native, Wong is an engineer, not a medical doctor, and has spent much of his career on the leading edge of rapidly advancing technology. In addition to his work on the automation of the inkjet printer and the online trading site Schwab.com, he helped develop the first 1 megabit VLSI (very large scale integration) computer memory chips and the first hospital-wide picture archiving and communication system (PACS). He is among the pioneers in bioinformatics, an emerging field that employs computers to store and analyze the enormous amount of genetic, imaging and clinical data now available online to scientists and physicians.
Since his arrival at Methodist, Wong’s team has mined a wealth of information, including databases on genetics, proteins, drug trials, scientific literature, and the FDA database on about 1,700 approved drugs and 3,800 experimental drugs in clinical trials.
While the traditional approach to developing a drug involves focusing on a target, such as a gene, and determining whether it is the culprit, Wong uses mathematical models and computer analysis to sort through vast amounts of data and tries to match existing drugs — or combinations of them — to diseases for which they weren’t originally designed. The candidate drugs, identified by computer analysis, are further validated with carefully designed biological experiments.
“It’s an upside-down way of approaching it,” Wong says. “We couldn’t have done this just a few years ago, but now the publicly available, NIH-funded clinical trial databases, as well as the advances in computers, enable us to sift through so much information.”
Another major benefit of using existing drugs is the dramatically shorter time needed to get them into use if they prove successful. With new drugs, the FDA’s three-phase process of clinical trials can take as long as 10 years. With existing drugs, however, researchers can avoid the Phase I trials, which can take three to five years. Collaboration spurs advances
Wong’s process has led to two encouraging studies in breast cancer cases in partnership with Dr. Jenny Chang, medical director at the Lester and Sue Smith Breast Center at Baylor College of Medicine. Chang had conducted biopsies on the tumors of some patients whose cancers had remained confined to the breast and on others whose cancers had metastasized to the brain. That occurs in about 12 percent of breast cancer cases and is incurable, Wong says.
Now, with computer modeling and analysis, Wong and his researchers are working to develop drug combinations that will be effective on specific types of tumors at different stages. Two drugs are in Phase II trials, and he also is conducting research on possible drug cocktails for cancers of the lung, prostate and brain. He compares the effort to directing an orchestra: managing many complex elements to achieve a harmonious outcome.
Wong has more than $15 million in National Institutes of Health funding to improve diagnostics and patient outcomes in the areas of neurodegenerative diseases and cancer.
The Methodist Hospital Research Institute was established in 2004 to conduct research in support of advancing patient care and raising medical practice standards. It now has more than 1,700 credentialed research team members, including more than 400 principal investigators conducting research in the most important areas of human disease.
More than 700 active clinical trials are under way at the Research Institute, and that number is expected to double by 2012. Since its inception, the Research Institute’s federal research funding has grown six-fold, a testament to its success in recruiting national and international leaders in critical research and research support areas. n
NIH AwARDS woNg $11.5 MILLION RESEARCH GRANT
The Methodist Hospital Research Institute was awarded an $11.5 million Center Grant by the National Institutes of Health to study the best approach to attack deadly cancer stem cells to enhance treatments for breast cancer. Other members of the team include Baylor College of Medicine and the University of Texas Health Science Center at Houston.
“Targeting cancer stem cells, rather than cancer cells, is a completely new strategy for treating cancer,” says Stephen Wong, Ph.D., director of the Center for Bioengineering and Informatics at The Methodist Hospital Research Institute and principal investigator for the grant study. “By attacking the cancer stem cell, we hope to eliminate cancer’s ability to grow, recur or metastasize.”
The NIH grant will enable Wong’s team to model breast cancer stem cells — or see what they look like and how they act — using advanced genetic, imaging and computer modeling techniques. Wong said once the cells are modeled in the lab and in real environments, the team will be able to predict the behavior of cancer stem cells, enabling them to test drugs that might kill the cells or prevent the cells from duplicating and metastasizing. Cancer stem cells have the ability to resist drugs, become cancer cells, and split into a cancer cell and another stem cell. Traditional cancer treatments use chemotherapy to kill cancer cells but are not optimized to kill the stem cell.
“Targeting the cancer stem cell is the new horizon for cancer research,” Wong says. “We have put together a very strong team of top experts in the field. We’re able to combine that talent with the technology at our disposal at Methodist, Baylor and UT. This is a formidable combination that has potential to achieve real breakthroughs in cancer research. It’s great to now have the backing of the NIH to help us move ahead.”
Besides providing a basic framework for understanding breast cancer stem cell evolution, the models will allow the team to predict how the natural process of cancer development will play out in various circumstances. The ultimate goal is better, more effective treatment for eliminating breast cancer. n
