Revealing metastatic tumor microenvironmental mechanisms in osteosarcoma to develop novel therapeutic approaches

The National Cancer Institute awarded the Research Institute At Nationwide Children's Hospital $146,779 on September 1, 2026, under the Cancer Biology Research program (CFDA 93.396) to investigate metastatic tumor microenvironmental mechanisms in osteosarcoma and develop novel therapeutic approaches.

The funded research identifies mechanisms underlying metastatic establishment in osteosarcoma by examining interactions between epithelial cells, macrophages, and tumor cells within the microenvironment. The work focuses on crosstalk among these cells in the lung that drives chronic wound response, fibrosis, and immune environment modulation. The research team has demonstrated proof-of-concept in mouse models of metastatic osteosarcoma using drugs targeting these signals, achieving dramatic reductions in metastatic burden, and is pursuing clinical translation of these findings. The work has applicability to other cancers with similar metastatic biology, including breast cancer that metastasizes to the lung. The award funds bioinformatic analysis and genomic approaches, with responsibility for downstream analysis, experimental guidance, and training of trainees within the research laboratory.

Performance occurs in Columbus, Ohio, with a period of performance extending from September 1, 2026, through August 31, 2031. This is a Project Grant, a competitive assistance mechanism under which applications are evaluated on scientific and technical merit, program relevance, and program balance consistent with National Cancer Institute and National Institutes of Health priorities.

Abstract

Osteosarcoma is a cancer that most frequently affects either the very young or elderly populations with around 1,000 new cases per year. Overall survival is ~60% for patients without metastatic disease at diagnosis. However, patients with multiple metastatic lesions have a 5-year event-free survival of less than 20%. This poor outcome is primarily due to a lack of effective treatments for metastatic osteosarcoma. The focus of our lab is to find treatments to address this deficiency. Specifically, using NCI funded grants, we are identifying mechanisms underlying metastatic establishment to reveal therapeutic vulnerabilities. We have shown that epithelial cells and macrophages have critical interactions with tumor cells within the tumor microenvironment. The crosstalk among these cells in the lung lead to a chronic wound response, fibrosis and modulation of the immune environment. Using drugs targeting these signals, we performed proof-of-concept experiments in mouse models of metastatic osteosarcoma and showed dramatic reduction of metastatic burden. We are pursuing efforts to clinically translate these findings. Our research has broad implications for other cancers that rely on similar biological mechanisms during metastasis. For instance, there are many parallels between our findings and published data on breast cancer, which also frequently metastasizes to the lung. DR. Cannon is an expert that bridges biological and computational research. He plays a critical role within the lab of ryan roberts and oversees all bioinformatic analyses. He is responsible for providing guidance for experiments utilizing genomic approaches and completing downstream analyses. He also mentors and teaches trainees within the roberts lab and more broadly across the center for childhood cancer research to foster the next generation of bioinformatics scientists. This application seeks funding to support DR. Cannon's ongoing work within the roberts lab to continue the pursuit of improved treatments for metastatic osteosarcoma. The important role filled by DR. Cannon will help to ensure the success of our current and future NCI funded research.