|
Research Directions: next
BIOLOGY OF DRUG RESISTANCE IN CANCER:
• Identification and characterization of NAC-1 (like BCL-6 as a BTB/POZ member) in ovarian cancer. NAC-1 expression is associated with tumor recurrence in ovarian cancer patients after optimal debulking and chemotherapy. Disruption of NAC-1 homomerization using the dominant negative strategy suppresses tumor growth and induces apoptosis in cancer cells with NAC-1 overexpression both in vitro and in vivo. Ongoing studies include the development of nanoparticle delivery system for dominant negative constructs (in collaboration with Johns Hopkins Nanomedicine Institute) and test the new reagent in treating mouse xenograft models. We also propose to assess the roles of NAC-1 in recurrent tumors from other organs including colorectum, pancreas, brain, lung and breast. Future studies will also focus on the mechanisms how NAC-1 contributes to chemoresistance or recurrence. Reference: 24
• Development of a drug resistance mouse model by passing ovarian cancer ascites cells directly from patients to mouse peritoneal cavity without tissue culture. The model has been established by us and modified to express a urine marker for non-invasive tumor monitoring using the method we previously established 25. The tumors that are resistant to taxol and carboplatin have been established in mice. Using this human ascites tumor model as a discovery tool, we currently focus on identification of molecular alterations associated with recurrent/chemoresistant tumors. SNP array, SAGE, expression arrays and microRNA profiling will be used. The molecular alterations will be prioritized and validated in matched primary and recurrent human ovarian serous carcinoma tissues. We expect to characterize the prioritized changes that are associated with tumor recurrence/chemoresistance in both biological and clinical context.
|
|
