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RESEARCH FOCUS: Pharmacological targeting of Metastatic Breast Cancer
Research in our lab is focused on understanding and targeting the molecular mechanisms necessary for cancer cells to exit the primary tumor environment, metastasize and acquire resistance to currently used targeted molecular therapies. Given their specificity is not surprising that while several targeted therapies are initially quite effective, metastatic tumor recurrence and therapeutic resistance remain major clinical problems. A critical aspect of metastasis and drug resistance is the process of epithelial-mesenchymal transition (EMT). EMT is a highly complex process whereby normal epithelial cells can temporarily take on characteristics of more motile and fibroblastoid like cells to facilitate developmental processes and wound repair. Cancer cells aberrantly utilize this process during tumor invasion and metastasis, and EMT is also linked to acquisition of a stem-cell phenotype and drug resistance. Recent work by our laboratory has depicted critical roles for EMT in primary tumor exit and initiation of outgrowth at the metastatic destination. Furthermore, we have established that EMT plays a critical role in altering signaling processes emanating from ErbB1 (EGFR) and ErbB2 (Her2), two key molecules in breast cancer development. These EMT-mediated events coalesce to elicit resistance to breast cancer therapies that target ErbB receptors. |
Understanding and overcoming how EMT facilitates resistance to ErbB-directed therapeutics is a major focus of our research. To approach this question we have established a number of unique cell lines that have undergone EMT and acquired resistance to agents targeting ErbB receptors and downstream effector molecules. Global gene expression analyses of these resistant cells have revealed several potential targets that may be responsible for the EMT process and more importantly therapeutic resistance. Ongoing work in the lab utilizes genetic and pharmacologic manipulation of several potential resistance mediators to validate their role in eliciting EMT and the drug resistant status of cancer cells. To address these questions we utilize approaches that include three-dimensional cell culture and in vivo mouse models of tumor growth and metastasis. In particular our research has a directed focus on utilizing in vivo optical imaging to track and quantify cell number, location and specific activation of particular signaling pathways.
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SUPPORT BREAST CANCER RESEARCH IN THE WENDT LAB: To support research happening in the Wendt lab gifts can be made to the Purdue Research foundation with a note indicating funds should be directed to the Lab of Dr. Michael Wendt. Gifts can be mailed to: Purdue University Center for Cancer Research Hansen Life Sciences Building 201 S. University St West Lafayette IN 47907 LAB NEWS December 2021 - Congrats to Hang Lin on successful defense of her dissertation, "Targeting FGFR in metastatic breast cancer." Good luck in your postdoc, Hang. You will be missed! May 2021 - Congrats to Hao Chen on receipt of the Bilsland Dissertation Fellowship. May 2021 - Congrats to Aneesha on receipt of the Interdisciplinary Graduate Programs Summer Research Grant! May 2021 - Welcome to the new graduate students, Aneesha Kullkarni, Brenna Vaughn, and Marvis Monteiro! February 2021 - Our publication on Transglutaminase-2 in extracellular vesicles was the "Best of Oncogenesis" for 2020. January 2021 - Fibroblast growth factor receptor facilitates recurrence of minimal residual disease following trastuzumab emtansine therapy; was published in NPJ Breast Cancer. Congrats Saeed! October 2020 - Epigenetic targeting of neuropilin-1 prevents bypass signaling in drug resistant breast cancer; was published in Oncogene. Congrats Ammara! October 2020 - Pharmacological inhibition of FGFR modulates the metastatic immune microenvironment and promotes response to immune checkpoint blockade; was published in Cancer Immunology Research. Congrats Saeed! October 2020 - SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer; was published in Oncogene. Congrats Hao Chen! |