Antibody-Mediated BRCC36 Silencing: A Novel Approach for Targeted Breast Cancer Therapy
Annual rept. 1 Jun 2009-30 May 2010
FOX CHASE CANCER CENTER PHILADELPHIA PA
Pagination or Media Count:
The significant mortality associated with metastatic breast cancer suggests a clear need to improve current therapeutic strategies. Breast tumor cells with defective BRCA1 are believed to be more sensitive to the DNA-damage based therapies. We propose that the aberrant expression gain or loss or activity of proteins in BRCA1-associated pathways will lead to a BRCA1 null-like phenotype and DNA damage hypersensitivity in breast cancer cells. Previous studies have demonstrated that BRCC36 is overexpressed in the vast majority of invasive breast cancers and that depletion of BRCC36 sensitizes breast cancer cells to IR via the BRCA1 DNA repair pathway. Therefore, we are examining if abrogation of BRCC36 will sensitize breast tumors to the DNA damage based therapies. We have tested a cancer cell-specific or smart therapeutic approach utilizing the conjugation of anti- HER2 antibodies and protamine to deliver BRCC36 siRNA to HER2 positive breast cancer cells. This approach should lead to improving the targeting of breast tumor cells while reducing non-specific toxicity.
- Medicine and Medical Research