Steven Sizemore Lab
My laboratory investigates the mechanisms that drive cancer metastasis and seeks to develop novel therapies for the treatment of metastatic disease.
The Sizemore Lab is currently funded by an NIH NCI K22 Career Development Award. Research in the lab combines analyses of data from human tumor samples with mouse models of cancer and mechanistic in vitro studies with the ultimate goals of 1) improving our ability to predict which tumors will metastasize; 2) providing a better understanding of the factors that guide organotropic metastasis; 3) identifying the molecular drivers of metastasis with emphasis on actionable targets; and 4) developing novel therapies for the prevention and treatment of metastases.
Currently, there are two primary foci in the laboratory. One studies metastasis of triple-negative/basal-like breast cancer (TN/BLBC) and the other examines metastasis of soft tissue sarcomas (STS).
Breast cancer therapies must be tailored to best attack each patient’s unique cancer. For women with metastatic TN/BLBC, there currently are few therapy options. Approximately 15% of all breast cancers are TN/BLBC, including most BRCA1-mutant breast cancers. This percentage is even greater in young and African-American women. TN/BLBC frequently metastasizes to the lungs and brain, and women with TN/BLBC have a significantly shorter survival time following metastasis compared to the other types of breast cancer.
Soft tissue sarcomas (STS) are a diverse collection of cancers of mesenchymal origin arising from the connective and supportive tissues of the body. While localized STS are well managed by surgery and radiation, metastasis, particularly to the lung, is frequent. More than 30% of adult STS patients develop lung metastases and the five-year survival for these patients is a dismal 16%.
Treatment options for metastatic TN/BLBC and metastatic STS are limited, thus there is an urgent unmet need for a better understanding of the key molecular pathways that drive metastatic spread of these cancers and identification of inhibitors of these pathways for clinical application. My laboratory has identified the RAL GTPase isoforms RALA and RALB as targetable drivers of metastasis in both TN/BLBC and STS. Ongoing research seeks to uncover the mechanisms through which the RAL proteins regulate metastasis and how to best target these molecules to provide innovative treatment for metastatic disease. Other projects focus on the roles of cancer secreted exosomes and their contents in metastatic progress and how treatment of the primary tumor may influence metastatic spread.