Angelina Vaseva, Ph.D.
Rank: Assistant Professor
Department: Molecular Medicine
Despite the high cure rates among children with cancer, following treatment with current multimodality therapies, survivors face profound lifelong therapy-related complications and thedevelopment of second malignancies, increasing chronic, life-threatening toxicities as they age. In addition, the survival rate for many high-risk pediatric cancer patients has not improved significantly over the last 30 years. Hopes for the future depend on identifying novel therapies targeting specific cancer-driving cellular and molecular mechanisms, ensuring improved survival for high-risk patients, and providing a better quality of life for survivors. Components of the RAS and ERK MAPK pathways are frequently deregulated in pediatric cancers, including leukemias, central nervous system tumors, and extracranial solid tumors. Our focus is to systematically define mechanisms of RAS and ERK MAPK- driven vulnerabilities in pediatric cancers and design directions for clinically relevant targeted therapeutic options. Toward these efforts, we employ a wide variety of in vitro cell-based assays, unbiased genetic and pharmacologic screens, as well as in vivo preclinical testing of patient-derived xenograft tumor models. Another focus of our research is to understand how the two oncogenes, RAS and MYC, cooperate to promote tumor cell growth and maintenance and how we can exploit this cooperation in order to design therapeutic strategies for RAS-driven pediatric cancers. We recently demonstrated that targeting MYC degradation in RAS-driven cancers circumvents treatment adaptation.
Further, we have determined that maintenance of MYC protein levels is context-specific and precise evaluation in each cancer type is required. By utilizing an MYC-degradation reporter, we aim to identify signaling pathways and druggable targets that regulate MYC protein stability in pediatric sarcomas. Further, we will exploit our discoveries to design novel targeted therapeutic strategies.
Shreetama Banerjee, PhD
Research Assistant Teresa Marple,PhD
Senior Research Associate
Arnab Sarkar, PhD,
Angelina Vaseva, PhD to Receive NCI Method to Extend Research in Time (MERIT)(R37) Award.