IBSC-BME PhD Defense Announcement for Brenna Vaughn (L. Solorio, advisor)
Everyone is invited to attend the public presentation beginning at 10:00am.
Title: Transglutaminase-2 Enables Actin-Microtubule Driven Resistance to T-DM1 in HER2-Overexpressing Breast Cancer Cells
Date:
Friday, June 6th
Time:
10:00am
Location:
MJIS 2001 and Zoom - https://purdue-edu.zoom.us/j/99831119513
Committee: Dr. Luis Solorio (Advisor), Dr. Michael Wendt, Dr. Leopold
Green, Dr. Hector Gomez
Abstract:
Recurrence and progression are important measures of efficacy in evaluating
cancer drugs. When cancer cells develop resistance to a therapy, cancer can progress or recur at sites local or distant to the treated disease. In recent decades, antibody-drug conjugates have improved the ability to target cancer cells and deliver chemotherapeutic
agents with higher specificity. However, recurrence and progression remain common with these drugs. In the present study, we describe a novel mechanism of resistance to the antibody-drug conjugate T-DM1 in HER2 overexpressing breast cancer cells. Although
there are several known mechanisms of resistance to T-DM1, it is not fully clear why T-DM1 preforms much worse than the newer drug T-DXd, the same targeting antibody with different cytotoxic payload. Addressing this knowledge gap is vitally important to inform
further research and development.
Cells become resistant when exposed exclusively to the cytotoxic payload of T-DM1 in the absence of the associated antibody, confirming resistance arising from
the microtubule inhibitor. Increasing density of cells and subsequently higher â1 integrin expression correlated with increasing survivability of escalating T-DM1 dose. Further, overexpression of the matrix stabilizing enzyme transglutaminase 2 (TG2) confers
a survival advantage in chronic T-DM1 exposure. Inhibition of focal adhesion kinase and myosin II reverses this survival advantage. These facts indicate an a-actinin as a key mediator of resistance. We thus demonstrate the role of TG2 and â1 integrin in HER2
overexpressing breast cancer cells in gaining resistance to T-DM1 via an actin cytoskeletal adaptive mechanism.
Zoom link:
Topic: Brenna Vaughn's PhD Defense
Time: Jun 6, 2025 10:00 AM Eastern Time (US and Canada)
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https://purdue-edu.zoom.us/j/99831119513
Meeting ID: 998 3111 9513
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Meeting ID: 998 3111 9513