Generating Drug Resistant 3D Organoids – UROP Spring Symposium 2024

Generating Drug Resistant 3D Organoids

Salem Wang

Pronouns: she/her

Research Mentor(s): Hamadi Madhi
Research Mentor School/College/Department: Internal Medicine / Medicine
Program:
Authors: Salem Wang, Jaselyn Porter, Hamadi Madhi , Habib Serhan , Sofia Merajver , Nathan Merrill
Session: Session 2: 10:00 am – 10:50 am
Poster: 99

Abstract

Drug resistance is a persistent challenge in cancer research. As cancer cells divide, some of them acquire mutations that render the drug treatment ineffective. These cells survive and continue to divide, resulting in disease progression. Therefore, unraveling the mechanisms that confer resistance is of great interest for improved cancer therapy. In this project, we developed 3D breast cancer organoids to mimic human tissue and made them resistant to a chemotherapy drug, Combretastatin A4 (CA4). CA4 is a naturally occurring well known tubulin polymerization inhibitor that causes microtubule depolymerization, inhibiting cell division and ultimately causing cell death. However, at low concentration and under a long-term exposure, some cells can develop resistance to CA4. By generating CA4-resistant organoids from two different triple negative breast cancer cell lines, MDA-MB-157 and SUM-52, this project opens the door to developing other CA4-resistant organoids, which constitute a more accurate model of breast cancer resistance to chemotherapy drugs that can be studied using traditional 2D cell cultures. These organoids can be used in genetic analyses to reveal the genes driving resistance development, thereby contributing to improvements in targeted therapy among breast cancer patients.

Biomedical Sciences, Interdisciplinary, Natural/Life Sciences

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