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Detection and Elimination of Oncogenic Signaling Networks in Premalignant and Malignant Cells with Magnetic Resonance Imaging

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Technical Report,30 Sep 2014,29 Sep 2015

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Duke University Durham United States

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The current paradigm for detection and treatment of breast cancer is based on clinical evaluation and anatomic imaging, usually with digital mammography or less commonly breast magnetic resonance imaging MRI, followed by biopsy and surgery or surgery plus radiotherapy. While both mammography and MRI demonstrate excellent sensitivity for detecting tissue abnormalities, they lack sufficient specificity for unequivocally distinguishing malignant from normal tissue, or for discerning highly aggressive from less aggressive neoplasms. Activation of oncogenic signaling nodes occurs prior to the growth of tumors to a size that is anatomically detectable or displaces adjacent tissue, and prior to invasion and metastasis. Detection of these early molecular changes is not possible with existing imaging technologies used for breast cancer screening, but will be possible with the development of a new class of molecular imaging as we propose. We hypothesize that novel PM small molecule inhibitors that selectively target key deregulated intracellular signaling nodes in breast cancer cells can be utilized for detection and molecular characterization of early stage breast cancers using MRI and for subsequent targeted RF-mediated thermal ablation of malignant cells in vivo. The goal of this work is to develop multicomponent molecules that deliver PM contrast agents to selected cellular systems through targeted non-covalent interactions with specific enzymes to improve breast cancer detection and treatment. We propose to detect and characterize oncogenic signaling nodes in breast cells in vivo, to transform breast cancer diagnosis, characterization, risk stratification, treatment and ultimately prevention

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