Drugs versus IBC: who will win?

Dr. Devi gave me some freedom during the beginning of the program to explore the work of other scientists in the lab to see what kind of research I would be interested in conducting. My interest lies in pharmacy; thus, I am interested in drug therapy and how certain diseases will react with certain drugs. I used my interest of pharmacy to design a project that suited my interest but at the same time would help the lab gain new knowledge.

One of the focuses of Dr. Devi’s lab is inflammatory breast cancer (IBC). IBC is a very aggressive form of breast cancer that forms no one solid tumor mass, but instead, forms characteristic diffuse tumor cell clusters which spread along the breast parenchyma and block lymph vessels. Furthermore, IBC is also known to affect minority populations and younger populations disproportionately and is thus an important health disparity issue. Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals emitted from incomplete organic fuel combustion, many of which are carcinogenic and linked to increased cancer risk at certain human exposure levels. In vitro studies with PAH chemical exposure in Dr. Devi’s lab have seen morphological and signaling pathway changes in breast cancer cells due to this exposure, wherein low-doses of PAHs can ultimately increase growth and survival of a panel of breast cancer cells.

The research I will be focusing on this summer is to validate the Devi lab 3D tumor emboli model for inflammatory breast cancer and to test the effects of an environmental chemical mixture on tumor emboli formation and/or pre-existing morphology using this model. Concurrent chemotherapeutic treatments may also be added in addition to this environmental chemical mixture to scratch the surface of understanding therapeutic resistance in these aggressive IBC emboli. The environmental chemical mixture is comprised of thirty-six PAHs characterized by mass spectrometry, and different concentrations of the mixture will be administered to an IBC cell line. Potential chemotherapeutic drug therapies to be used concurrently are U0126 (a lab-grade ERK inhibitor), Eloxatin (a topoisomerase inhibitor), and Trastuzumab/Herceptin (a HER2 inhibitor). These three different drugs all have different inhibition targets, but their overall goal is to restrict cancer cell proliferation and promote apoptosis. I can’t wait to see the results I will get from these experiments, and to share them with the BSRUF and Duke community.

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