Bone metastases are a common site for the spread of solid cancers, yet their histological and molecular characteristics remain largely unexplored. A recent study published in Cell Genomics by researchers from Baylor College of Medicine and the University of Texas MD Anderson Cancer Center uses RNA sequencing to analyze bone metastases from eight different cancer types, identifying three distinct immune ecosystem archetypes.
Dr. Xiang H.-F. Zhang, co-corresponding author and director of the Lester and Sue Smith Breast Center at Baylor, stated, “Bone metastases vary widely from person to person, yet all bone metastases are treated similarly with treatment targeting one cell type, osteoclasts. Some patients do not respond to this treatment. In this study, we examined the heterogeneity of bone metastases across different cancer types and within each cancer type.”
The research team, including Dr. Robert L. Satcher from MD Anderson, collected 42 samples of bone metastases across various cancer types. Satcher noted the collaboration allowed them to approach the problem with a unique perspective: “The interesting finding is that there are both similarities and differences that are cancer-type specific.”
RNA sequencing revealed three immune ecosystem archetypes: macrophages and osteoclasts; regulatory and exhausted T cells; and monocytes. The researchers validated these findings using existing RNA sequencing data from 158 bone metastases spanning ten cancer types.
Findings showed that the identified archetypes did not always align with tumor origins. Metastases from identical cancer types often belonged to different archetypes while those from diverse cancer types sometimes shared an archetype. This suggests both convergent and divergent evolutionary pathways in cancer development.
The study suggests exploring varied treatment strategies tailored to each archetype could be beneficial. For instance, treatments activating exhausted T cells might be more effective than traditional anti-osteoclast therapies for certain archetypes.
First author Fengshuo Liu emphasized potential therapeutic targets identified within each archetype for further validation: “Our data is all publicly available, and many groups are already using it for other studies.”
Zhang highlighted the significance of pan-cancer research: “This study highlights the power of pan-cancer research. The border of different cancer types becomes blurred when they all come to the same place in the bone.”
Contributors to this work include several researchers affiliated with Baylor College of Medicine, MD Anderson Cancer Center, and University of Texas Medical Branch.
Funding was provided by various organizations including the U.S. Department of Defense, National Cancer Institute, Breast Cancer Research Foundation, Cancer Prevention and Research Institute of Texas, and National Institutes of Health.
