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Identification of novel therapeutic approaches to treat breast cancer metastases
My lab focuses on developing new treatment approaches to treat patients with existing metastatic disease. There are several genetically distinct types of breast cancer and we mainly study triple-negative breast cancers (ER-/PR-/HER2-), especially those defined genetically as basal-like as they grow fast and metastasize to the brain, lung, and liver. Basal-like breast cancer is nearly always treated with chemotherapeutics; unfortunately, many tumors acquire resistance to chemotherapies, and different treatment options are needed. To study this in the lab, we have developed a set of patient-derived xenograft (PDX) models that are sensitive or resistant to chemotherapy, and ongoing studies are utilizing drug screens, bulk/single-cell RNA-sequencing, and proteomics to identify approaches to bypass this drug resistance (National Cancer Institute funded). Some of the PDXs have ‘clinically actionable mutations’ in some genes and could potentially be treated with drugs that target these activating mutations; we are interested in identifying secondary inhibitors that synergize with these mutation-targeting drugs, mimicking the NCI ComboMATCH trial (Susan G. Komen funded). Since people of different ethnicities often get different types of breast cancers, we are incorporating PDXs from different ethnicities to identify genetic differences that make contribute to treatment effectiveness (Massey Cancer Center funded). Other collaborative studies are seeking to use Artificial Intelligence to help select synergistic drug combinations (Loren Picco Lab; Jeffress Trust), incorporate single-cell RNA-sequencing (Dozmorov lab; VCU School of Medicine funded), further develop High Speed Live Cell Interferometry for therapeutic drug selection (Jason Reed lab), and identify new approaches for advanced ER+ disease.