Dubbed with the name Profile, this program has been almost two years in development and is said to be one of the most extensive research projects in cancer genomics yet undertaken nationally in the United States—with the study design leaving it open to every adult cancer patient seen in the BWH and Dana-Farber Longwood Medical Area clinics.
"Profile will put us firmly on the path to realizing the promise of personalized medicine," says Dr. Barrett Rollins, Dana-Farber's chief scientific officer. "By genotyping each tumor—identifying the set of mutations that drive it—we'll be able to design therapies geared specifically to those mutations, depriving the tumor of the ability to sustain itself while producing a minimum of side effects."
Rollins, one of the architects of Profile, says he and the other designers of the program expect the study to grow quite a bit over time as Dana-Farber and BWH discover new cancer-related gene mutations and as new technologies are developed during the course of the study, whether at those two institutions or elsewhere. As Rollins describes it, the program design is "less a permanent fixture than an infrastructure that allows us to install new technologies as they become relevant."
Under the current parameters and study design, tissue-testing for the program will be performed with OncoMap, a system custom-designed for genomic research in cancer by investigators at Dana-Farber and the Broad Institute of MIT and Harvard. This approach will bring into play
high-speed, high-capacity robotic machinery to prepare, sort and scan tumor tissue and the system will, Rollins says, enable researchers to quickly process large numbers of tumor tissue samples with a high degree of accuracy.
"We've learned a great deal about the role of specific mutated genes in cancer, and we now have technology for testing large numbers of tumor samples for those mutations," notes Dr. Janina Longtine, director of molecular diagnostics at BWHl and a senior leader of the research program. "For the first time, we have the opportunity to build a critical mass of genomic data that can be used to bring better treatments to patients."
Other key leaders within Profile include Dr. Monica Bertagnolli of BWH and Dr. Philip Kantoff of Dana-Farber.
While the first goal is to give all of Dana-Farber's and BWH's adult cancer patients a chance to have their tumor tissue scanned for genetic mutations that are known or suspected of being linked to cancer—with a goal of using the database in studies that seek to improve the effectiveness, safety, and precision of cancer treatments—there is another key aspect as well. That second aspect will focus on familial cancer risk. As part of that effort, patients will be asked if they wish to donate normal, non-cancerous cells from their body for studies of inherited gene mutations that increase people's risk of developing certain cancers at a young age.
"The explosion of genomics research means that every patient has something to contribute to the defeat of cancer," Rollins says.
Profile is designed to be distinct from other programs that often looks at particular types of tumors, with an eye toward small number of gene mutations. In contrast, Profile will test tumor samples for nearly 500 cancer mutations in 41 genes, and the program's leaders predict that more than 10,000 people will participate in the program during the first year and every year thereafter.
"In cancer, we can't afford to overlook any source of information," Bertagnolli stresses. "Early on, we realized that this project wouldn't work as a small-scale, 'boutique' effort. Without a global approach—analyzing the tumors of every patient who consents—we would be limiting our ability to make major breakthroughs."
"The data will allow us to analyze the links between specific mutations and tumor behavior to an extent that has never before been possible," Kantoff adds. "We'll have the opportunity to make observations that can spark a whole new array of clinical trials."
Dana-Farber is contributing $35 million to the effort, with BWH contributing approximately $8 million of its own.
"Ultimately, our goal is to bring cancer treatment fully into the era of personalized medicine, in which treatment addresses the specific genetic composition of each patient's tumor," Rollins explains.