Investigating Mutant SF3B1 as a Novel Therapeutic Target in Breast Cancer
Abstract
The future of cancer treatment lies in precision oncology: targeting particular drugs to particular patients. But since 1998, when researchers scored a major victory for targeted cancer therapy with the approval of the breast cancer drug Herceptin, no other drugs tied to specific gene mutations in breast cancer have been approved. We see targeted drugs like these as crucial players in the fight against breast cancer, and here we propose to focus on targeting mutations in a gene called SF3B1. SF3B1 shows up mutated in 2% of breast cancers, or over 30,000 patients each year worldwide. The mutations cause RNA missplicing: where messages from the cell s DNA instruction manual are jumbled on their way to making the proteins that do the cell s work. This missplicing likely ends up making abnormal proteins that drive cancer growth and gets in the way of making enough healthy proteins that keep tumors from growing. But we believe this missplicing also has an Achilles heel, presenting new kinds of targets for cancer therapy -- therapy that would be more specific and less toxic than what we have now. This project would give me, as a postdoctoral physician-scientist, expertise in a promising area of breast cancer science that is now understudied. With the resources of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, and the support of the Park Lab, I believe I could take that understanding to the next level by developing therapies against these targets, and initiating clinical trials to test them in patients, perhaps within 5 years. What s more, the approaches I learn here could also apply to other kinds of RNA abnormalities in cancer cells. Studies have found that at least 10%-20% of breast tumors have some degree of RNA missplicing, so the implications could be significant.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1710035
Entities
People
- Brian Dalton
Organizations
- Johns Hopkins University
- United States Army