Connective tissue tumors
During a recent checkup at Dana-Farber, Sarah Russell of Palmer, Mass., chats with sarcoma expert George Demetri, MD.
Sarcomas are unique among the major categories of cancer in that they strike a relatively small number of people but take many forms. They arise in the tissues that hold the body together: bones, tendons, cartilage, muscle, deep layers of skin, fat, and blood vessels. There are an estimated 12,000 new sarcoma cases in the United States each year, and literally dozens of varieties. Some forms can easily be cured, while others are lifethreatening (see related sidebar).
The cells that give rise to sarcomas are among the most primitive in the body, their job the unglamorous work of anchoring other tissue, supporting weight, and providing energy, storage, and structure. When such cells become cancerous, the changes they undergo may reflect something fundamental in the cancer process—closer to what underlies all cancers than the complex changes found in other types of cancer called "carcinomas."
"From a research perspective, sarcomas are intriguing because they involve the basics of what turns cells cancerous," Demetri says. "I'm interested in how we can exploit this for the benefit of patients. The fact that sarcomas form by a relatively simple, direct process means that shutting down a single gene pathway may disable an entire tumor. And if that particular gene is involved in sarcomas, there's a good chance it may contribute to other types of cancer as well."
It's not surprising, then, that many standard cancer therapies—among them the chemotherapy drug methotrexate, developed by Dana-Farber founder Sidney Farber, MD—initially proved effective in sarcoma. "Sarcomas have often been a bellwether for cancer treatments," Demetri adds.
Yet for all they may reveal about the fundamental workings of cancer, sarcomas pose a major challenge to researchers. Their relative rarity, coupled with their diversity of forms, means it can be difficult to recruit enough patients, or collect enough tumor samples of one type, to conduct valid studies of new therapies.
Here, the major treatment centers clearly have an advantage, and the Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) has established one of the largest sarcoma practices in the country. The Sarcoma Center at the DF/BWCC receives referrals for approximately 800 new sarcoma patients a year, about 500 of whom participate in clinical research studies of novel treatments—numbers that put DFCI, BWH, and their affiliates high on the partner list for biotech and pharmaceutical companies developing new medications. Dana- Farber's clinical trials are generally run with Dana-Farber/Partners CancerCare, a research alliance with Brigham and Women's and Mass. General hospitals; the three currently have more than 650 sarcoma patients enrolled in these experimental protocols.
"At any given time, we have approximately 50 new sarcoma drugs at various stages of development, from basic laboratory research, to work in tissues and animals, to studies in patients," Demetri says. "About 20 of those drugs are currently being evaluated in different phases of clinical trials.
"Our work with biotechnology and pharmaceutical firms is changing the model by which sarcoma therapies are developed," he continues. "In the past—before the Human Genome Project and the explosion of knowledge about gene pathways underlying cancer—we might approach a pharmaceutical firm with the question, 'Do you have a compound that kills sarcoma cells?' Often, the company would say that since this was an uncommon tumor type, there was no economic incentive to develop such a drug. The success of Gleevec has changed that mindset. Today it's a more collaborative process. Our understanding of the basic biology of sarcomas enables us to identify the specific genes and pathways that therapies should target. Biotech firms develop chemicals to hit those targets; our team works in the laboratory to confirm the targeting, and we do research to determine potential benefits for patients."
Demetri hopes the partnership will be responsible for the rapid introduction, testing, and approval of several new sarcoma drugs in the next two years—at a rate unprecedented in the history of this disease.
What follows is a brief look at a few key members of Dana-Farber's sarcoma research team.
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