Probing metabolic alterations in breast cancer in response to molecular inhibitors with Raman spectroscopy and validated with mass spectrometry.

Chemical Science
Xiaona WenRizia Bardhan

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 nonresponsi...Continue Reading

References

Oct 24, 2006·Pharmacogenomics·Kristine Glunde, Natalie J Serkova
Jun 10, 2008·Cancer Cell·Guido Kroemer, Jacques Pouyssegur
Jan 30, 2010·Cancer Metastasis Reviews·Kelly K Haagenson, Gen Sheng Wu
Jun 23, 2011·Molecular Systems Biology·Ori FolgerTomer Shlomi
Dec 17, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·M Pia MorelliS Gail Eckhardt
Jan 13, 2012·Cell Death & Disease·C Muñoz-PinedoJ-E Ricci
Mar 24, 2012·Cancer Cell·Patrick S Ward, Craig B Thompson
Jul 18, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Steven J PottsHolger Lange
May 7, 2013·Cancer Treatment Reviews·Kamal S SainiMartine J Piccart-Gebhart
Aug 2, 2013·Science Translational Medicine·Moshe ElkabetsJosé Baselga
Sep 4, 2013·The Journal of Clinical Investigation·Ming YangPatrick J Pollard
Jan 13, 2015·The Journal of Membrane Biology·Izabela DobrzyńskaZbigniew A Figaszewski
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale
Jan 26, 2016·Oncogenesis·S Beloribi-DjefafliaF Guillaumond
Mar 22, 2016·Chemical Society Reviews·Isaac Pence, Anita Mahadevan-Jansen
Jul 8, 2016·Science Advances·Ralph J DeBerardinis, Navdeep S Chandel
Jul 30, 2016·Frontiers in Oncology·Natalie J Serkova, S Gail Eckhardt
Aug 31, 2016·Analytical Chemistry·Anil Kumar Meher, Yu-Chie Chen
Nov 23, 2016·Cancer Discovery·Claudio VernieriValter Longo
Jan 14, 2017·Frontiers in Oncology·Menglin ChengKristine Glunde
Aug 23, 2017·Applied Spectroscopy·Faris SinjabIoan Notingher
Nov 18, 2017·Nature Reviews. Cancer·Besim Ogretmen
Mar 30, 2018·Archives of Pathology & Laboratory Medicine·Seshi R SompuramSteven A Bogen
May 17, 2019·British Journal of Cancer·Rimsha MunirNousheen Zaidi
May 17, 2019·Nature Reviews. Urology·S Larry GoldenbergSeptimiu E Salcudean
May 18, 2019·Cancers·Bo-Hyun Choi, Jonathan L Coloff
May 18, 2019·Annals of Biomedical Engineering·Despoina N MetsiouGeorge Athanassiou
May 24, 2019·International Journal of Molecular Sciences·Iris C SalaroglioChiara Riganti
Sep 4, 2019·Scientific Reports·Abdullah Saif MondolIwan W Schie
Oct 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela BovenkampAngelika Unterhuber
Oct 17, 2019·The Analyst·Thomas James Eliot HubbardNicholas Stone
Nov 2, 2019·Nature Communications·Chi-Sing HoJennifer Dionne
Nov 24, 2019·Cancers·Amaia Eleonora MaennlingAhmad Fawzi Hussain

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Methods Mentioned

BETA
PCA
electrophoresis
SPLASH

Clinical Trials Mentioned

NCT03971409
NCT03395899
NCT02155088
NCT02998476
NCT01241500

Software Mentioned

Python
Metabolika
MATLAB
Renishaw WiRE
GraphPad Prism
Compound Discoverer

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