Posted: February 22, 2012

CASE STUDY: From the Bedside to Bench and Back Again

Emma J. Spaulding

Image: Dr. Adam Bass, M.D., Physician-Scientist at the Dana-Farber Cancer Institute and member of the TCGA Research Network

The “Bench to Bedside” translational science philosophy is the theory that science should progress from discovery at the lab bench, through the establishment of scientific evidence, through commercialization, to administration at a patient’s bedside. Broadly, this means sticking to a unidirectional path that begins in a research laboratory and ends with treating a patient.

However, Adam Bass, M.D., Physician-Scientist at the Dana-Farber Cancer Institute and member of The Cancer Genome Atlas (TCGA) Research Network, imagines a different philosophy: a bedside to bench and back to bedside principle, which he has applied to his career, his lab and his daily life.

Dr. Bass recognizes that he has always been interested in both research and patient care. During medical school he knew that he wanted to incorporate research into his career, but wasn’t sure how to do it. He realized that he didn’t want to be primarily a clinician or researcher. He admits that he didn’t have the patience to spend decades focused upon a specific gene or pathway in depth, “which is why I would not have been a good traditional academic scientist,” he says.

A Changing Landscape

It was during Dr. Bass’ clinical training that the cancer research community had begun to see the early successes derived from analysis of cancer genes. These findings lead to better therapies. Dr. Bass says, “There’s the now-classic textbook example of this, such as the use of imatinib to block a particular genomic translocation in a subtype of leukemia… Those [drugs] were emerging at this time and I saw the landscape with more of these opportunities.”

While Dr. Bass was training in clinical oncology at the Dana-Farber Cancer Institute, he met Matthew Meyerson, M.D., Ph.D. Dr. Bass says Dr. Meyerson “has been instrumental in helping to develop these [genomic] technologies and applying them to cancer and cancer therapeutics. Basically, picking the right drug for the right patient based on the genome. It was an example of a type of work I wanted to build towards.” So, Dr. Bass moved from the bedside to the bench. During the 4 years of his post-doctoral fellowship in cancer genomics, he worked with Dr. Meyerson to develop several studies on Dr. Bass’s area of interest, gastrointestinal cancer. 

With this new experience, Dr. Bass realized that he liked being able to attack cancer with the dual perspective of a physician and a scientist. He says, “It made it easier for me to think more broadly and more creatively about how to use a wide array of resources and approaches to address a very broad question – how to better understand these tumors.”

In 2010, Dr. Bass left the Meyerson lab to create his own research group at the Dana-Farber Cancer Institute with the goal of focusing on gastric and esophageal cancer. “When I was working in my clinical training and thinking where to go next in research, I was trying to think of where I can more likely make an impact.” During his clinical oncology fellowship, Dr. Bass had seen deadly cases of esophageal and gastric cancer, and an absence of treatment options. Discussing the state of esophageal and gastric cancer research at the time, Dr. Bass says, “There was relatively little data, so it seemed like an opportunity where we could make more progress.” Though therapies based on cancer genome analysis were being developed for other cancers, he adds that “technologies weren’t being as quickly applied to these diseases and the need was huge, given how poor the survival is for these cancers.”

Embodying the bedside to bench and back again philosophy, the Bass lab comprises researchers and clinicians and maintains active collaborations with the Broad Institute. He says they work to bring the findings from a patient’s cancer genome into the laboratory. With deeper study, the group hopes to validate therapeutic targets and collaborate with clinical scientists to identify drugs that can be tested in clinical trials. He summarizes by saying, “We can use these incredible new genomic data to develop new therapeutic opportunities for our patients.”

Becoming a TCGA Investigator

TCGA expanded to include more cancers in 2010 and soon after, Dr. Bass joined the data analysis group of the colorectal project. Specifically, he was analyzing data to define areas of the genome that were lost or amplified. When discussion of starting a project for esophageal cancer began, he helped champion the effort. “Its very important," he says, "given our lack of knowledge, rising incidence, and horrible survival rate.”

Naturally, once the research project was established, Dr. Bass was given the opportunity to co-lead with Ilya Shmulevich, Ph.D. Dr. Bass has also maintained a longstanding interest in gastric cancer, and so, when TCGA formed a gastric cancer project, he was offered co-leadership of the gastric cancer project by Peter Laird, Ph.D. He accepted both of these positions.

Dr. Bass believes that genomic research in gastric and esophageal cancer is just beginning. He describes the TCGA research projects as “a huge opportunity but that analyzing and building off of these data will prove a substantial challenge. The genomes of these cancers are extremely complex. We do not have a sufficiently developed framework of pathways and models upon which to apply these data. We have many years of work ahead of us at the computer and at the bench to nail down the most critical genes and pathways in these cancers and then to figure out how to use that knowledge to advance clinical care.”

These days, Dr. Bass enjoys the best of working at a hospital and engaging in research. He spends most days in his laboratory but still spends some time each year at the bedside, caring for cancer patients during their time in the hospital. He enjoys working “to apply science to clinically relevant problems” and describes himself as a scientific primary care doctor.

Dr. Bass hopes that his lab will contribute to the analysis of the genomic data. He’d like to expand his laboratory into translational science and eventually, clinical trials. He explained that he’d like to grow so that “we can take some of these findings and start to move towards new clinical use of these targets.”