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Boston Center to Leverage NGS Capabilities of Broad, Tumor Profiling at Dana-Farber for Cancer Patients

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A new Boston clinical cancer genomics center will leverage resources from the Broad Institute, the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and the Boston Children's Hospital in order to figure out how to best integrate molecular profiling and genomics in cancer care and treatment.

The Joint Center for Cancer Precision Medicine will make use of a number of different tools, relying heavily on next-generation sequencing.

"Profiling tumors for genetic and molecular changes that can help guide therapy is going to be an important path forward in cancer, but I think it's fair to say that the full understanding of how to prosecute cancer precision medicine has not been worked out," Levi Garraway, the new center's director and an associate professor at Dana-Farber, told Clinical Sequencing News.

Challenges remain, related both to infrastructure and also carrying out the translational science to understand where this type of information will and will not be useful, he added.

Garraway told CSN that there will be three components of the center. First, he said, it will be important to "beef up infrastructure" that will allow for serial biopsies to be performed at various stages of disease such as pre- and post-treatment. Second, a strong clinical computational portion will be important for rendering sequencing and other types of genomic data useful for physicians and to help correlate that data with patient response to drugs. And finally, the center will have a strong translational laboratory component in order to create patient-derived cell lines to study drug response and resistance, and other experiments so that "we can understand with a more rapid turnaround what is going on," he said.

The center will make use of space at all of the founding institutes, he said. For instance, he said, certain activities will take place at Brigham and Women's Hospital because that is where many biopsied specimens are processed, while much of the genomic profiling activity and next-gen sequencing will take place at the Broad Institute. The center will also take advantage of the clinical trials run at Dana-Farber.

Garraway said that he expects to "leverage heavily" the Broad's sequencing capabilities, in particular, its recently-established CLIA-certified Clinical Research Sequencing Platform, or CRSP, through which it can offer exome sequencing on the Illumina HiSeq 2500. Garraway said that the Broad has other CLIA sequencing services in development, including an RNA-seq pipeline, which the center will make use of as they become available.

The center will also be involved in the Profile project currently ongoing at Dana-Farber to molecularly characterize patients' tumors. Profile was initially launched in 2011 and used a targeted mass spec-based technology called OncoMap to genotype patients' tumors, but this summer transitioned to a targeted sequencing panel of 305 genes. Testing is done at the Center for Advanced Molecular Diagnostics, a CLIA-certified laboratory at Brigham and Women's Hospital.

Additionally, the center will support a study of how exome sequencing of cancer patients may be helpful to oncologists, Garraway said. Known as CanSeq, the study aims to sequence the exomes of 200 lung cancer and 200 colon cancer patients and will analyze the results over the next two years.

Garraway said the researchers are addressing the questions of what information to return to oncologists as well as the practicalities of generating and interpreting that information in a relevant time frame.

Thus far, Garraway said that one of the main challenges has been "the ability to robustly curate a whole exome." Currently, analyzing data and determining what data is clinically relevant is a very manual, time-consuming process that involves a tumor board that reviews each case. But in any given meeting, said Garraway, a board may only get through a couple of patients, creating a backlog.

As such, he said one goal is to identify ways that will enable this to be done much more quickly, including building a knowledge base of variants that will allow much of the process to be automated.

Another option is to do a "first-pass curation" quickly and put in place a mechanism for the oncologist to request a consultation if a more detailed interpretation is needed, Garraway said.

Recently, the researchers also received funding from the Stand Up to Cancer Initiative to include prostate cancer patients in the CanSeq study. Garraway said CanSeq will continue to be broadened in a targeted way with breast cancer most likely next on the list. "We want to do this in such a way so that we have particular questions for each disease," he said.

Overall, Garraway said that the new center will impact both current patients as well as help to guide research studies that will make a difference for future patients.

"In many cases we would expect to be able to use the [genomic] information to guide the next round of treatment. We're designing this to make that possible," he said. Additionally, the data will also help inform future clinical trials and studies. For instance, he said, we might learn if we were to biopsy a patient prior to treatment, during treatment, and after relapse, that although the targeted drug did hit the target, adaptive changes happened during treatment that make the drug work less well.

While that data may be useful for the particular patient, it is more likely that the data will inform a new clinical trial, for instance, one that uses combination therapy to overcome the drug's waning effectiveness.

"The goal certainly is to use the data in as much as it meets our current understanding to help guide the next therapeutic choice for a patient, but equally, there's a lot more to learn in terms of how we need to design new therapeutic combinations and how they need to be given to achieve more lasting control," Garraway said.

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