Engineering Ambassador at University of Iowa College of Engineering Office of Admissions
August 2017 - May 2018
CELL RESPONSE TO FLUID SHEAR STRESS EXPOSURE PREDICTS DRUG TREATMENT SUCCESS IN METASTATIC MELANOMA PATIENTS
Honors Thesis Abstract:
The cancer drug vemurafenib (VEM) targets a mutation called BRAF+ found in two thirds of metastatic melanoma cases. Within BRAF+ cells, VEM targets and interrupts a cellular pathway, leading to cell death and tumor shrinkage. However, of these BRAF+ patients, approximately 50% do not respond to VEM. This occurs despite the fact that resistant patients have melanoma with the same genetic profile as responsive patients. With no way to genetically distinguish between resistant and responsive melanoma, common practice is to treat all metastatic melanoma patients presenting as BRAF+ with VEM initially.
It is known that the same cellular pathway interrupted by VEM also regulates cancer cell membrane dynamics. Cells that are responsive to VEM have less resilient membranes because the necessary cell pathway has been compromised. Therefore, VEM-responsive cells are more easily destroyed when exposed to certain forces, such as fluid shear stress (FSS). FSS occurs when layers of fluid move past each other, inducing stress in the fluid that is passed along to anything flowing within it. In this study, both resistant and responsive melanoma cells were treated with VEM, suspended in a liquid, and placed in a device to produce controlled levels of FSS. Analysis of the change in cell viability after FSS exposure supported the hypothesis that FSS sensitivity is an indicator of VEM sensitivity. This predictive method could be expanded and refined for use on clinical patient samples to better determine candidates for VEM treatment and develop targeted therapies for BRAF+ metastatic melanoma patients.
May 2020 -
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