Proteomic and Metabolic Reprogramming in Myeloma Cells within the Tumor Microenvironment

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Background

Multiple Myeloma (MM) is an incurable cancer of plasma cells primarily resident in the bone marrow. Due to extensive antibody production, MM cells crucially rely on the protein quality control pathway; and must cope with a high metabolic expenditure and proteosynthetic, oxidative and degradative stress. The strict and intricate crosstalk interaction with the other immune and non-immune cell components of the bone marrow microenvironment features MM disease and supports MM cell survival, drug-resistance and immune evasion. The clinical success of proteasome inhibitors and immunomodulatory agents highlights these dependencies and has transformed the treatment paradigm and patient outcome. However, patients eventually relapse; and a deeper understanding of MM complex biology is needed to guide the discovery of more effective targeted therapies and inform clinical management.

The goal of this special issue is to elucidate and discuss the metabolic hallmarks of MM cells, their roles in early and late stages of MM development and progression, and how they could be exploited for therapeutic purposes. Understanding the molecular basis of MM metabolic rewiring will allow for a better understanding i) of its role in key metabolic processes such as mitochondrial respiration, lipids, glucose and amino acid consumption and protein homeostasis and degradation; ii) and of the complex crosstalk between hypoxic and acidic bone marrow microenvironment and MM cells. The identification of novel MM-specific metabolic signatures may shed light on the mechanisms of drug resistance and immune evasion and explore the therapeutic potential of new metabolic drugs.

This Research Topic will focus on proteomic and metabolic reprogramming in myeloma cells and how it shapes the interaction with immune and non-immune components of the tumor microenvironment. We aim to dissect the metabolic circuits of MM in order to define novel therapeutic approaches and inform clinical management. We welcome submissions on the following areas and we particularly encourage Original Research, Review and Clinical Trials.:
- Proteomic and/or metabolic rewiring of MM cells
- Role of proteomic and/or metabolic changes in precursor stages of disease and in MM progression
- Role of proteomic and/or metabolic changes in drug resistance
- Role of proteomic and/or metabolic changes in the crosstalk with immune and non-immune components of bone marrow microenvironment

Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology

Keywords: Myeloma, Metabolism, proteostasis, plasma cells, microenvironment

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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