Although sarcomas are not nearly as common as cancers of the breast, prostate, colon, or lung, they often strike people in the prime of life-particularly children, adolescents, and young adults. As a result, the number of years of life lost is substantial.
While progress has been made in extending survival, sparing limbs, and preserving form and function for many patients with sarcoma, each tumor is quite distinct genetically, requiring a targeted approach to therapy. Better drug treatments are needed, fueled by research into the biology of these tumors. Perlmutter Cancer Center investigators are working to delineate the molecular basis of sarcomas with the goal of identifying new therapeutic targets. Such research includes:
Investigations pinpointing certain pathways that drive sarcoma development and growth. The drug trabectedin (ET-743)-approved in Europe and under investigation in the United States for treating soft-tissue sarcoma (including a pediatric clinical trial at the Perlmutter Cancer Center)-interferes with cancer cell division by binding to a groove in a cancer cell's DNA.
Perlmutter Cancer Center scientists are exploring which cells become sarcoma cells and how they do it. They have been studying how alterations in microRNAs-tiny pieces of RNA which don't have the ability to encode proteins, like regular RNA, but which are involved in gene expression and the normal maintenance of tissues-might impair the maturation of stem cells, leading to tumors such as leiomyosarcoma (a tumor that arises in the uterine wall).
Our investigators have developed a mouse model that replicates the development of sarcoma in patients, breeding mice that lack copies of the tumor suppressor genes PTEN and p53, which normally put the brakes on rampant cell growth. These mice eventually develop sarcomas that metastasize to the pancreas, liver, and lung (the most common sites of metastasis in people). Such mouse models enable scientists to identify genetic mutations that drive sarcoma growth -- information that can help clinicians identify more effective therapies.
Many sarcomas may look the same clinically or under the microscope, and are currently treated in the same way. But they may have very different genetic properties. The more scientists know about their molecular biology, the better they can tailor personalized treatments for patients. Perlmutter Cancer Center researchers are therefore studying sarcoma tissue obtained from patients before and after treatment to analyze mechanisms of tumor response to treatment and factors that promote resistance to therapy.