Inga-Marie Schaefer, MD
Brigham and Women's Hospital
CIC-rearranged sarcoma: biologic mechanisms and therapeutic targeting
Grant Sponsor
Dr. Schaefer is studying an aggressive cancer called CIC-rearranged sarcoma, common in children and young adults. CIC-rearranged sarcoma has a poor response to chemotherapy and poor survival. Understanding its mechanisms is crucial to developing an effective therapy. By creating new cell lines and models, Dr. Schaefer’s Powered by Pablove project aims to identify what drives this cancer’s development. Her goal is to find vulnerabilities and cell cycle abnormalities that could lead to effective treatments for this often misunderstood cancer.
In Dr. Schaefer’s own words:
CIC-rearranged sarcoma is an aggressive soft tissue neoplasm that frequently affects children and young adults. CIC-rearranged sarcoma exhibits very aggressive clinical behavior with a median overall survival of only 12 months and poor response to chemotherapy. This highlights the urgent need to generate a better understanding of the oncogenic mechanisms of CIC-rearranged sarcoma and identify biologic vulnerabilities for therapeutic targeting. The lack of reliable preclinical models has thus far prevented therapeutic advances. To overcome this limitation, our group recently created the first-ever patient-derived CIC-rearranged sarcoma cell lines and murine xenografts. Our goal is to identify oncogenic mechanisms and biologic vulnerabilities that drive CIC-rearranged sarcoma development and progression, ultimately leading to the development of effective therapeutic strategies. In this proposal, we aim to leverage our model systems of CIC-rearranged sarcoma to characterize the oncogenic mechanisms of perturbations of the cell cycle machinery and validate our findings in patient samples. We hypothesize that CIC-rearranged sarcomas are characterized by cell cycle pathway aberrations promoting tumor growth and that such pathway perturbations render CIC-rearranged sarcomas sensitive to targeted therapies. Our team of talented investigators is uniquely positioned to pursue the proposed research.