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Mark Kieran's laboratory selects promising agents and evaluates them in human tumors which have been orthotopically implanted into mice. This process quickly moves potential therapies into the clinic. At present, more than five such projects are ongoing in conjunction with different groups at Dana-Farber Cancer Institute, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, and Children's Hospital.
In conjunction with a number of groups, Kieran and colleagues have examined a series of tumor specimens from adult and pediatric patients to evaluate the expression of abnormal signaling pathways. The increasing availability of small-molecule inhibitors of many cell-surface signaling receptors may open the door to a series of clinical trials. To date, this work has focused on the pathways of the epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR), and ErbB2 receptor. The first national clinical trial based on this work is already underway.
In collaboration with the laboratory of Dr. Judah Folkman, Kieran's group has initiated experiments that examine the antiangiogenic effects of a number of available agents, such as endostatin, as well as others whose activity involves novel pathways. As these agents enter clinical trials--either alone or in combination with standard chemotherapy or radiation--their spectrum of activity and toxicity can be better defined. This work also focuses on developing a series of surrogate markers of activity for these agents, so that their use in humans can be optimized for antitumor activity.
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