Recently, progress has been made in developing new and effective personalized molecular therapies with minimal side effects that are useful in some tumors. Recent advances by MD Anderson sarcoma physicians include:
Gastrointestinal stromal tumors (GIST). Some of these tumors, a specific sarcoma subtype, can now be effectively treated with imatinib (Gleevec). Prior to imatinib, there was no effective systemic treatment for this disease. Physicians in the Sarcoma Center were instrumental in the GIST success story, which gives us hope that these approaches can be extended to other types of sarcoma. For an example of how this research has benefited patients, read Richard Lobo's story.
Biomarkers. Research published in 2007 in the Proceedings of the National Academy of Sciences identified a technique to distinguish between genetic biomarkers for leiomyosarcoma (LMS) tumors and gastrointestinal stromal tumors (GIST) with near-perfect accuracy, making rapid treatment decisions and treatment response predictions possible.
Chemotherapy effectiveness. When patients do not respond to chemotherapy, often it is because a mutated DNA repair protein (Rad51) is at abnormally high levels. Preclinical studies are currently evaluating methods to decrease Rad51 levels in sarcomas.
The p53 growth-regulating gene. When the p53 gene is altered through mutation, degradative proteins known as matrix metalloproteinases (MMPs) are no longer suppressed and provide a molecular means for tumor cells to penetrate blood vessels and spread. In preclinical studies, introduction of normal p53 into sarcoma tumors with the mutated p53 gene causes marked reduction of MMP production and a corresponding decrease in tumor spread.
Anti-angiogenesis. One way to restrict tumor growth and metastasis is to disrupt the tumor’s ability to make and recruit blood supplies (angiogenesis). For human leiomyosarcoma and synovial sarcoma, researchers have shown that the same p53 gene therapy will suppress angiogenesis and thus reduce tumor growth.
Adaptation of isolated limb perfusion. Researchers are testing a proven delivery system to administer new molecular therapies. Isolated limb perfusion is currently used to place high doses of chemotherapy precisely at a tumor site in an arm or leg. Blood flow is temporarily interrupted using a pump recirculator, much like a cardiac bypass machine, allowing direct treatment delivery.