Demetri's Team Approach Translates Into Success in Sarcoma Research

Published: Wednesday, Feb 10, 2016
George D. Demetri, MD

George D. Demetri, MD

For some cancer researchers, success means running your own laboratory independent of others, who might be viewed as competitors. Others, like George D. Demetri, MD, find success pursuing a career as a translational and clinical investigator, in which his goal is to bring other researchers together into highly functioning teams of global collaborations across academia, government, biopharma, and philanthropic enterprises.

His collaborative leadership has led to remarkable advances in the treatment of sarcoma, particularly the sarcoma subtype known as gastrointestinal stromal tumor (GIST).

“I was once told by a well-meaning mentor, ‘You are smart enough, you could run your own lab, but you are throwing your career away to be a clinical investigator.’ Traditionally, laboratory investigators are set up as the really smart guys. But that was not the role I chose to pursue,” said Demetri, recipient of the 2014 Giants of Cancer Care® award in Gastrointestinal Cancer.

Rather than spending his time in the laboratory, Demetri views himself more as a matchmaker, “making connections between faculty members, research nurses, and our various research teams in the experimental therapeutics program here at the Dana-Farber Cancer Institute, across Harvard Medical School, and extending into many other sectors of research, development, and care delivery.

I bring people together and make sure that our projects and programs are moving forward— whether they focus on GIST or other subtypes of sarcomas, whether they are in early or late clinical trial stage, or in expansion cohorts to other diseases,” said Demetri.

This approach to teamwork has been fruitful, says Demetri, who is the senior vice president for Experimental Therapeutics at the Dana-Farber Cancer Institute and a professor of Medicine at Harvard Medical School in Boston, Massachusetts.

This teamwork approach has extended to productive collaborations with start-up biotechnology companies such as Sugen and Plexxikon in the past, according to Demetri.

“Initially, this approach didn’t appear to fit the outdated standard concepts in which academicians ask basic questions. Also, biopharma companies are in the business of implementing studies to get drugs approved,” Demetri said. The lack of overlap in these separate worlds seemed inefficient and poorly designed for the modern era of mechanism-based drug discovery and more precise and predictive therapeutic development; Demetri thought if academicians could drive the science behind the trials in collaboration with top-notch companies, then nearly magical efficiencies and effectiveness could be achieved.

“The foremost example of our team’s work has been the sequential development of uniquely different tyrosine kinase inhibitors as effective therapies for patients with GIST. By targeting specific molecular structural variants of GIST, we have validated the concept that a human solid tumor can be treated by signal transduction inhibitors,” Demetri said.

He has designed and implemented a worldrenowned clinical research center focused on the treatment of sarcomas, and his team is at the cutting edge of developing personalized cancer therapeutics for several uniquely defined subtypes of sarcomas.

Their efforts helped lead to the development and subsequent FDA approval of imatinib mesylate (Gleevec) as the first effective therapy for patients with metastatic or unresectable GIST, and serves as the basis for ongoing research into other novel agents. The development of Gleevec, one of the first examples of a rationally targeted oral cancer therapy for a solid tumor, was followed by research to overcome drug resistance through other targeted drugs, including sunitinib (Sutent) and regorafenib (Stivarga) for GIST as well as pazopanib (Votrient) for other sarcomas.

Evolving Sarcoma Research

Sarcomas are a paradigm of the complexity and heterogeneity of solid tumor oncology. Clinically important subsets of sarcomas are increasingly being defined by molecular signatures and biological characteristics rather than by the part of the body in which the disease arose. Demetri’s team is translating this research about the basic biology of sarcomas into new therapeutics directed at novel targets.

“The biggest change in sarcoma research is that we have discarded the notion that there is one thing called ‘sarcoma,’” said Demetri. Sarcoma has been parsed into hundreds of different diseases, Demetri continued. “If we really understand the wiring in all the tumors, we might be able to make some difference for patients.”

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Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize OutcomesOct 31, 20182.0
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