Charlotte McLean with Dr. Cesar Martin Castro (MGH)
Nanotechnology offers novel methods to diagnose, profile, and treat gynecologic cancers. In particular, Extracellular Vesicles (EV) can be utilized to profile cancer pathology. EV’s are cell-derived phospholipid vesicles, including exosomes, microparticles, and apoptotic bodies, which are naturally released from cells, both benign and malignant. They are a heterogenous group of circulating vesicles, ranging in size from 20 nm to 2,000 nm, and carry a broad range of cargo including proteins, nucleic acids, and lipids which are indicative of their origin cell. EV’s travel in the extracellular environment and are known to facilitate intercellular communication throughout the body. From a clinical perspective, these circulating EV’s can be used as biomarkers to profile cancer pathology in patients. We are utilizing EV’s to better understand and treat Breast Cancer, particularly the highly aggressive and metastatic Triple Negative Breast Cancer (TNBC), which is defined by the absence of estrogen and progesterone receptors and low levels of HER2 protein. Taxane treatment is a standard Breast Cancer chemotherapy drug, particularly for TNBC. Paclitaxel, a taxane, causes cell death by stabilization of microtubules during mitotic processes, inhibiting a cell’s ability to disassemble. However, paclitaxel resistance among TNBC is high, leading to low response rates and recurrence. At the Im and Castro Lab, we are utilizing the role of EV’s as biomarkers for early detection of taxane resistance. We are using interdisciplinary approaches including cellular immunostaining, flow cytometry, size exclusion chromatography, and bead-based EV flow cytometry. These methods are being used to better understand biomarkers including HER2, EGFR, MUC1, and EpCAM and whether these are present in the EV’s of metastatic cells. The current goal of the project is to assess whether these biomarkers, and potentially newly identified biomarkers, are i) present in the EV’s of breast cancer cells ii) whether EV based biomarkers are altered due to paxlitaxel therapy, and finally iii) if EV based biomarkers are altered by chemotherapy resistance.
