Therapeutic Targeting of Alternative Translation Initiation in Breast Cancer
Abstract
I discovered that cap-independent translation of oncogene mRNAs, e.g. c-myc or vascular endothelial growth factor (VEGF) transcripts, is regulated by affinity of the eukaryotic initiation factor (eIF4G) for sequences within the 5 untranslated region of such mRNAs. Our work contributes to understanding how translation initiation factors, phosphoproteins controlled by the major oncogenic signaling pathways in cancer, regulate gene expression at the translational level. My findings enable functional studies of eIF4G and how it responds to protein kinase inhibitors currently tested in cancer therapy, e.g. against breast cancer. Most importantly, my work contributes key empirical evidence in support of a novel experimental cancer treatment scheduled to enter clinical investigation within the next 6 months. Cell type specific cancer cell killing of the prototype oncolytic poliovirus, PVS-RIPO, depends on selective eIF4G:IRES binding in cancerous cells. My work provided the empirical basis behind this principle and constitutes a critical aspect of correlative studies demanded by FDA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA552948
Entities
People
- Constanze Kaiser
Organizations
- Duke University Hospital