Collaborative initiative set up to create precision medicine treatment pathways for advanced cancers

Dana-Farber, Brigham and Women's, Boston's Children's Hospital and Broad Institute to collaborate to harness genetic data for patients

The Joint Center for Cancer Precision Medicine, a collaborative initiative among Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston Children's Hospital, and the Broad Institute of MIT and Harvard, has been established to create "precision medicine treatment pathways" for patients with advanced cancers and to speed the development of personalized therapies.

The Joint Center brings together expertise and resources in state-of-the-art capabilities including DNA sequencing and other tumor molecular profiling technologies, pathology, radiology, surgery, computational interpretation, and new tumor model systems; and reinforces the joint commitment to pursue advances in cancer genetics to improve patient care. It will be headquartered at Dana-Farber.

"This center will allow us to be optimally positioned to answer the big questions in cancer genetics, especially as they affect clinical decision-making," said Levi Garraway, MD, PhD, associate professor of medicine at Dana-Farber and the new center's director. "We seek to understand which genetic and other molecular alterations predict how tumors will respond to targeted drugs, why some patients become resistant to drugs, and what that means about the treatments that should be tried next."

"Our mission is to accelerate the development of personalized therapies that achieve long-term disease control and, eventually, the cure of many patients with advanced cancer," Garraway said. The terms "precision" and "personalized" both refer to an emerging form of cancer care that identifies genetic changes within a patient's tumor that can be used to predict how it will behave and which drugs will be most effective against it.

"The center is creating a new capability to use these huge resources in sequencing and pathology and making sure the data gets to caregivers to help customize treatment," said Edward Benz, Jr., MD, president of Dana-Farber.

"This exciting collaboration will allow the life-giving breakthrough of advanced genetic analysis of cancer to be translated into clinical care," said Betsy Nabel, MD, president of Brigham and Women's Hospital (BWH). "Patients will benefit from having the latest genetic discoveries applied to an individual treatment plan that will make a difference in their care."

"This is an extraordinary moment in biomedicine," said Eric Lander, PhD, president and director of the Broad Institute. "By learning from genomic information obtained in the course of clinical care of patients, this remarkable new center will be poised to make critical discoveries, and to ensure that those discoveries get translated back to the clinic."

A key part of the center will be a program to obtain and characterize new biopsies of patients' tumors during their treatment. Scientists will study the DNA, RNA, and protein in the biopsy samples to understand better how cancers respond or become resistant to drugs. In addition, some of the specimens will be used to generate cancer cell lines in the laboratory.

"This center will allow us to learn which genetic changes are driving each patient's cancers, how the changes occur, and when in the course of each patient's cancer care these genetic changes exert their effects," said Neal Lindeman, MD, director of the Center for Advanced Molecular Diagnostics laboratory in the BWH Department of Pathology. "All of this information can be used to design treatments that are more effective from the beginning and can be used to anticipate the changes each cancer will make during treatment, in the hopes of staying 'one step ahead' of the disease over time."

"The new center represents an exciting step forward on the path toward developing more treatments tailored to the particular characteristics of a child's cancer," said Katherine A. Janeway, MD, MMSc, a pediatric oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center (BCH). "Pediatric cancers often differ substantially from adult cancers, and the new center advances our ability to understand the genetic profile of childhood malignancies and ultimately better serve our young patients."

The center will keep Dana Farber/Brigham and Women's Cancer Center at the forefront of precision cancer medicine. Center leaders add that they are hopeful the joint center will win additional large-scale research grants from the federal government, industry, and philanthropy to help move the field forward.

Scientists will partner with leaders of the two-year-old Profile cancer genetics research project. That program currently sequences the DNA in 305 cancer-related genes of consenting adult and pediatric cancer patients at DFCI, BWH and BCH. Some of these DNA alterations can be targeted by drugs being tested in clinical trials.

In addition, Garraway leads a study called CanSeq, which sequences the entire "exome" - thousands of genes that carry recipes for proteins but aren't known to be involved in cancer. CanSeq will become an integral part of the new center, with scientists studying the value of costly whole-exome sequencing in cancer care.

"We want to find out how useful this would be - maybe it's too much information, or not enough," said Garraway. CanSeq researchers are in the process of sequencing the whole exomes of 50 lung and colon cancer patients as part of the pilot study.

Because genome sequencing produces a massive amount of data, the new center will create a computational biology group working in spaces at DFCI, the Broad, and BWH. It will include biologists, bioinformaticians, and software engineers to pioneer new algorithms for processing and interpreting the data provided by sequencing.

These institutions will also support a translational innovation laboratory for a variety of studies on "actionable" cancer mutations, drug resistance, and preclinical studies of targeted drug combinations.

"Ultimately, all of this is for patients," Garraway said. "We need to figure out how to leverage this very exciting time to forge what may be a new way of practicing cancer medicine."