American Association for Cancer Research

Developing New Therapeutic Strategies for Soft-tissue Sarcoma


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 will die from their disease. Wagers’ 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 introduces into these cells specific genetic modifications associated with human sarcomas. Using this model, she 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. Wagers hypothesizes that this novel set of sarcoma-induced genes includes new candidate drug targets. She will evaluate a library of drugs that target her identified sarcoma-associated genes, and identify those that prevent or impede sarcoma development, growth or metastasis. These efforts will benefit from synergistic analyses in her established mouse model and an entirely new, humanized system that will allow her to interrogate the efficacy of candidate therapeutics in an appropriate human cell context. This approach will generate essential preclinical data to facilitate clinical translation of candidate pharmaceutical targets identified and validated by her studies. 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.


Amy J. Wagers, Ph.D., is associate professor in the department of stem cell and regenerative biology at Harvard University and Harvard Medical School, and is a Howard Hughes Medical Institute early-career scientist.

Updated: April 4, 2011