Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment
Abstract
Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2022
- Source ID
- 10.3390/cancers14030757
Entities
People
- Adeline B. Ding
- Cristina Sánchez-de-Diego
- David J Beebe
- David Kosoff
- Erika Héninger
- Joshua M. Lang
- Nan Sethakorn
- Ravi Chandra Yada
- Sheena C. Kerr
Organizations
- Istituto Superiore di Sanità
- National Institutes of Health
- United States Department of Defense
- United States Department of Veterans Affairs