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.
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
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 - Sherry successfully defended her masters thesis. Congrats Sherry!
October 2020 - SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer; was published in Oncogene. Congrats Hao Chen!
March 2020 - Dr. Wendt has been selected as a regular member of the Tumor Progression and Metastasis (TPM) study section at the NIH. Congrats Dr. Wendt!
February 2020 - Saeed successfully defended his PhD dissertation, "Pharmacological targeting of FGFR signaling to inhibit breast cancer recurence and metastasis." Congrats Dr. Salehin Akhand!