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Proteometabolomics of Melphalan Resistance in Multiple Myeloma

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Metabolomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1996))

Abstract

Drug resistance remains a critical problem for the treatment of multiple myeloma (MM), which can serve as a specific example for a highly prevalent unmet medical need across almost all cancer types. In MM, the therapeutic arsenal has expanded and diversified, yet we still lack in-depth molecular understanding of drug mechanisms of action and cellular pathways to therapeutic escape. For those reasons, preclinical models of drug resistance are developed and characterized using different approaches to gain insights into tumor biology and elucidate mechanisms of drug resistance. For MM, numerous drugs are used for treatment, including conventional chemotherapies (e.g., melphalan or l-phenylalanine nitrogen mustard), proteasome inhibitors (e.g., Bortezomib), and immunomodulators (e.g., Lenalidomide). These agents have diverse effects on the myeloma cells, and several mechanisms of drug resistance have been previously described. The disparity of these mechanisms and the complexity of these biological processes lead to the formation of complicated hypotheses that require omics approaches for efficient and effective analysis of model systems that can then be interpreted for patient benefit. Here, we describe the combination of metabolomics and proteomics to assess melphalan resistance in MM by examining three specific areas: drug metabolism, modulation of endogenous metabolites to assist in therapeutic escape, and changes in protein activity gauged by ATP probe uptake.

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Acknowledgments

This work was supported by the Proteomics & Metabolomics and Cancer Informatics Cores at Moffitt, which are partially funded by the NCI Cancer Center Support Grant (P30-CA076292) and by Moffitt’s Innovation and Technology Pilot Funding (JK/KS). The SECIM at UF is funded by the NIH through U24-DK097209.

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Author notes

  1. David C. Koomen, Joy D. Guingab-Cagmat, and Paula S. Oliveira contributed equally to this work.

Authors and Affiliations

  1. Moffitt Cancer Center, Tampa, FL, USA

    David C. Koomen, Paula S. Oliveira, Bin Fang, Min Liu, Eric A. Welsh, Mark B. Meads, Tuan Nguyen, Steven A. Eschrich, Kenneth H. Shain & John M. Koomen

  2. University of Florida, Gainesville, FL, USA

    Joy D. Guingab-Cagmat, Laurel Meke & Timothy J. Garrett

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  1. David C. Koomen
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Correspondence to Timothy J. Garrett or John M. Koomen .

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  1. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    Sanjoy K. Bhattacharya

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Koomen, D.C. et al. (2019). Proteometabolomics of Melphalan Resistance in Multiple Myeloma. In: Bhattacharya, S. (eds) Metabolomics. Methods in Molecular Biology, vol 1996. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9488-5_21

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  • DOI: https://doi.org/10.1007/978-1-4939-9488-5_21

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