Tierney, Ciara and Bazou, Despina and Majumder, Muntasir M. and Anttila, Pekka and Silvennoinen, Raija and Heckman, Caroline A. and Dowling, Paul and O’Gorman, Peter (2021) Next generation proteomics with drug sensitivity screening identifies sub-clones informing therapeutic and drug development strategies for multiple myeloma patients. Scientific Reports, 11 (1). ISSN 2045-2322

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Abstract

With the introduction of novel therapeutic agents, survival in Multiple Myeloma (MM) has increased in recent years. However, drug-resistant clones inevitably arise and lead to disease progression and death. The current International Myeloma Working Group response criteria are broad and make it difficult to clearly designate resistant and responsive patients thereby hampering proteo-genomic analysis for informative biomarkers for sensitivity. In this proof-of-concept study we addressed these challenges by combining an ex-vivo drug sensitivity testing platform with state-of-the-art proteomics analysis. 35 CD138-purified MM samples were taken from patients with newly diagnosed or relapsed MM and exposed to therapeutic agents from five therapeutic drug classes including Bortezomib, Quizinostat, Lenalidomide, Navitoclax and PF-04691502. Comparative proteomic analysis using liquid chromatography-mass spectrometry objectively determined the most and least sensitive patient groups. Using this approach several proteins of biological significance were identified in each drug class. In three of the five classes focal adhesion-related proteins predicted low sensitivity, suggesting that targeting this pathway could modulate cell adhesion mediated drug resistance. Using Receiver Operating Characteristic curve analysis, strong predictive power for the specificity and sensitivity of these potential biomarkers was identified. This approach has the potential to yield predictive theranostic protein panels that can inform therapeutic decision making.

Item Type:	Article
Additional Information:	Cite as: Tierney, C., Bazou, D., Majumder, M.M. et al. Next generation proteomics with drug sensitivity screening identifies sub-clones informing therapeutic and drug development strategies for multiple myeloma patients. Sci Rep 11, 12866 (2021). https://doi.org/10.1038/s41598-021-90149-y
Keywords:	Multiple Myeloma; proteomics; sub-clones
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17269
Identification Number:	https://doi.org/10.1038/s41598-021-90149-y
Depositing User:	Paul Dowling
Date Deposited:	01 Jun 2023 14:12
Journal or Publication Title:	Scientific Reports
Publisher:	Nature
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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