Sarcomas are highly aggressive cancers that arise in connective tissues such as bone, fat, and cartilage, as well as in muscles and blood vessels embedded within these tissues. Approximately 12,000 Americans are diagnosed with sarcoma each year. These tumors can occur at any age, but many (e.g., rhabdomyosarcoma) are disproportionately common in children and young adults.
Current sarcoma treatment strategies are often ineffective, particularly with advanced disease, and sadly, even with the most advanced therapies currently available, one-third to one-half of sarcoma patients die from their disease. Dr. Wagers’s lab has developed a novel mouse model of soft-tissue sarcoma in skeletal muscle. This model exploits her lab’s unique ability to isolate discrete subsets of tissue stem cells found normally in the skeletal muscle and the connective tissue surrounding it, and to introduce into these cells specific genetic modifications associated with human sarcomas.
Using this model, Dr. Wagers found that introduction of a particular combination of modifications into distinct types of tissue stem cells rapidly and reproducibly generates transplantable sarcomas that model particular subtypes of human tumors. By comparing these different tumors, she has identified a small group of genes present at increased levels in both mouse and human sarcomas.
Dr. Wagers hypothesizes that this novel set of sarcoma-induced genes includes new candidate drug targets. She is evaluating a library of drugs that target her identified sarcoma-associated genes and identifying those that prevent or impede sarcoma development, growth, or metastasis. These efforts benefit from synergistic analyses in her established mouse model and an entirely new, humanized system that allows her to interrogate the efficacy of candidate therapeutics in an appropriate human cell context.
This approach is generating essential preclinical data to facilitate clinical translation of candidate pharmaceutical targets identified and validated by Dr. Wagers’s research. Ultimately, this work will identify new, more effective anti-sarcoma therapies based on a better understanding of how these cancers arise and grow, provide new insights into the root causes of sarcoma formation, and identify new strategies to cure these aggressive cancers.