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  • Paths of Progress Spring/Summer 2012

    The Osteosarcoma Researcher's View

    Seeking new treatments for pediatric sarcomas
    By Richard Saltus

    Katherine Janeway, MDKatherine Janeway, MD 

    It's often a challenge to develop drugs for rare forms of cancer; they are not widely studied, and recruiting enough patients for clinical trials is difficult.

    In these cases, "the key is understanding the biology of the disease," says Katherine Janeway, MD, a pediatric oncologist at Dana-Farber/Children's Hospital Cancer Center. Her goal is better treatments for osteosarcoma, a bone cancer that often strikes teenagers.

    "Progress in patient care is going to be very dependent on laboratory discoveries," says Janeway, who heads the Dana-Farber/Children's Hospital Cancer Center bone tumor program, where she cares for patients. She also conducts research in a Dana-Farber laboratory, probing the biology of osteosarcoma.

    Every year in the U.S., osteosarcoma affects 400 children under age 20, as well as 200 young adults. Approximately one-third of these 600 will ultimately die from the disease. The cancer is treated with surgery – sometimes requiring amputation – and chemotherapy.

    "There have been no new drugs for osteosarcoma in the last 25 years," says Janeway. "There haven't been a lot of breakthroughs in identifying targetable genetic mutations."

    Osteosarcoma develops near the ends of long bones, such as the thigh bones or the arm, during rapid growth. The tumors include primitive-looking bone-forming cells that grow chaotically, rather than differentiating normally into specialized types of cells and tissues.

    Some drugs force primitive, malignant cells to "grow up," forming differentiated tissues and curtailing their growth. Janeway asks, "Can we find a drug that can push osteosarcoma to look more like normal bone? If so, we could combine the drug with standard chemotherapy."

    Using a method developed by Dana-Farber/Children's Hospital Cancer Center pediatric oncologist Kimberly Stegmaier, MD, Janeway has begun testing a group of 1,500 existing drugs, to see if they can force osteosarcoma cells to differentiate. So far, she says, some promising candidates have been identified and are under further evaluation.

    "If we don't find anything, we'll have to move on to a much wider screen that includes compounds that aren't FDA-approved," she notes. Failing that, it will be all the more important to search for clues within the cancer cells.

    "We don't know enough about the basic biology of what blocks differentiation in osteosarcoma tumors," explains Janeway. "We don't know which gene pathway we should be targeting."

    Because industry might not be willing to invest a lot in the search for a new drug for such a rare disease, says Janeway, "I think you can really argue that if you can't find an existing drug, osteosarcoma is the type of disease where the initial work to develop a new therapy would need to be done in an academic environment such as Dana-Farber."

    Read how pediatric physician-scientists at Dana-Farber/Children's Hospital Cancer Center are collaborating with researchers around the world on sarcoma clinical trials.

    Paths of Progress Spring/Summer 2012 Table of Contents 

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