Campus Units

Chemical and Biological Engineering, Nanovaccine Institute

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Published Version

Publication Date

8-20-2020

Journal or Book Title

Chemical Science

Volume

11

Issue

36

First Page

9863

Last Page

9874

DOI

10.1039/D0SC02221G

Abstract

Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen. In this work, we demonstrate a rapid, noninvasive, and label-free approach to evaluate treatment response to molecular inhibitors in breast cancer (BC) cells with Raman spectroscopy (RS). Metabolic reprogramming in BC was probed with RS and multivariate analysis was applied to classify the cells into responsive or nonresponsive groups as a function of drug dosage, drug type, and cell type. Metabolites identified with RS were then validated with mass spectrometry (MS). We treated triple-negative BC cells with Trametinib, an inhibitor of the extracellular-signal-regulated kinase (ERK) pathway. Changes measured with both RS and MS corresponding to membrane phospholipids, amino acids, lipids and fatty acids indicated that these BC cells were responsive to treatment. Comparatively, minimal metabolic changes were observed post-treatment with Alpelisib, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, indicating treatment resistance. These findings were corroborated with cell viability assay and immunoblotting. We also showed estrogen receptor-positive MCF-7 cells were nonresponsive to Trametinib with minimal metabolic and viability changes. Our findings support that oncometabolites identified with RS will ultimately enable rapid drug screening in patients ensuring patients receive the most effective treatment at the earliest time point.

Comments

This article is published as Wen, Xiaona, Yu-Chuan Ou, Galina Bogatcheva, Giju Thomas, Anita Mahadevan-Jansen, Bhuminder Singh, Eugene C. Lin, and Rizia Bardhan. "Probing metabolic alterations in breast cancer in response to molecular inhibitors with Raman spectroscopy and validated with mass spectrometry." Chemical Science 11, no. 36 (2020): 9863-9874. DOI: 10.1039/D0SC02221G. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

Copyright Owner

The Royal Society of Chemistry

Language

en

File Format

application/pdf

Share

COinS