Targeted Therapies for Myeloma and Metastatic Bone Cancers
Abstract
Multiple myeloma is the second most common adult hematologic malignancy accounting for 1-2% of cancer-related deaths with 80% of these patients suffering devastating and progressive bone destruction. New treatment strategies are of urgent and vital importance. Several proteasome inhibitors are effective against both human and murine myeloma cells in culture and some have been shown to affect osteoblast differentiation and bone formation in rodents. However, as with any proteasome inhibitor, there are serious concerns over their potential systemic effects and toxicity. There is need to preferentially deliver these and other drugs to the bone microenvironment. The scope of this project is to determine, in preclinical studies, the potential of skeletally targeted PIs as an efficacious and selective treatment for myeloma. The program hypothesis is that bone-targeting nanocarriers can preferentially accumulate in the skeleton and locally release PIs to impair the capacity of myeloma cells to survive and grow in vivo, thereby reducing the formation and growth of tumor-induced lytic bone lesions. Proteasome inhibitors are not selective to bone and their therapeutic-toxic window may be narrow when administered systemically. Targeted bone delivery has potential to reduce systemic exposure, increase efficacy in the bone environment, and the opportunity to reverse catastrophic disease processes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA454700
Entities
People
- Neal Vail
Organizations
- Southwest Research Institute