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Current Oncology
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Dawn of a New Era in the Microenvironment-Targeted Treatment for...
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Dawn of a New Era in the Microenvironment-Targeted Treatment for Multiple Myeloma

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 9813

Special Issue Editors

Dr. Rikio Suzuki

E-Mail Website
Guest Editor
Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan
Interests: multiple myeloma; small-molecule inhibitors; myelomagenesis; chemoresistance; tumor microenvironment
Dr. Daisuke Ogiya

E-Mail Website
Co-Guest Editor
Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan
Interests: multiple myeloma; small-molecule inhibitors; myelomagenesis; chemoresistance; tumor microenvironment

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is an incurable hematopoietic malignancy originating from plasma cells. The outcome of multiple myeloma treatment has improved dramatically with the introduction of novel agents such as proteasome inhibitors, immunomodulatory drugs, and immunotherapies. In particular, elucidation of the onset mechanism of myelomagenesis and drug resistance mechanism using the latest analytical technologies is accelerating the development of these agents. As a result, in some cases, it has become possible to achieve a complete response or minimal residual disease negativity that can be said to be almost curable. Importantly, MM cells are known to manipulate the bone marrow microenvironment by altering the expression pattern of cytokines and biasing the diversity of cells in the bone marrow, finally leading to drug resistance. Therefore, the further expansion of drug discovery targeting the bone marrow microenvironment, partly focused on cell adhesion mediated drug resistance (CAM-DR) caused by the interaction between MM cells and bone marrow stromal cells, is being eagerly attempted. To provide curative therapies in the future, it may be necessary to discuss the possibility of treatment targeting myeloma-specific cellular elements such as inflammatory stromal cells and immunosuppressive cells. This Special Issue will highlight some translational aspects of research on the treatment targeting the MM microenvironment.

Dr. Rikio Suzuki
Dr. Daisuke Ogiya
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple myeloma
  • microenvironment
  • chemoresistance
  • CAMDR
  • inflammatory stromal cell
  • immunosuppressive cells
  • proteasome inhibitor
  • immunomodulatory drug
  • immunotherapy
  • novel drug

Published Papers (3 papers)

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Review

15 pages, 1070 KiB  
Review
Molecular Crosstalk between Chromatin Remodeling and Tumor Microenvironment in Multiple Myeloma
by Chandraditya Chakraborty and Srimoyee Mukherjee
Curr. Oncol. 2022, 29(12), 9535-9549; https://doi.org/10.3390/curroncol29120749 - 5 Dec 2022
Cited by 2 | Viewed by 2955
Abstract
Multiple myeloma (MM) is a complex disease driven by numerous genetic and epigenetic alterations that are acquired over time. Despite recent progress in the understanding of MM pathobiology and the availability of innovative drugs, which have pronounced clinical outcome, this malignancy eventually progresses [...] Read more.
Multiple myeloma (MM) is a complex disease driven by numerous genetic and epigenetic alterations that are acquired over time. Despite recent progress in the understanding of MM pathobiology and the availability of innovative drugs, which have pronounced clinical outcome, this malignancy eventually progresses to a drug-resistant lethal stage and, thus, novel therapeutic drugs/models always play an important role in effective management of MM. Modulation of tumor microenvironment is one of the hallmarks of cancer biology, including MM, which affects the myeloma genomic architecture and disease progression subtly through chromatin modifications. The bone marrow niche has a prime role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the ecosystem between multiple myeloma bone marrow microenvironment and chromatin remodeling. Extensive gene expression profile analysis has indeed provided the framework for new risk stratification of MM patients and identifying novel molecular targets and therapeutics. However, key tumor microenvironment factors/immune cells and their interactions with chromatin remodeling complex proteins that drive MM cell growth and progression remain grossly undefined. Full article
(This article belongs to the Special Issue Dawn of a New Era in the Microenvironment-Targeted Treatment for Multiple Myeloma)
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31 pages, 1384 KiB  
Review
Treating Multiple Myeloma in the Context of the Bone Marrow Microenvironment
by Matthew Ho, Alexander Xiao, Dongni Yi, Saurabh Zanwar and Giada Bianchi
Curr. Oncol. 2022, 29(11), 8975-9005; https://doi.org/10.3390/curroncol29110705 - 21 Nov 2022
Cited by 12 | Viewed by 3997
Abstract
The treatment landscape of multiple myeloma (MM) has evolved considerably with the FDA-approval of at least 15 drugs over the past two decades. Together with the use of autologous stem cell transplantation, these novel therapies have resulted in significant survival benefit for patients [...] Read more.
The treatment landscape of multiple myeloma (MM) has evolved considerably with the FDA-approval of at least 15 drugs over the past two decades. Together with the use of autologous stem cell transplantation, these novel therapies have resulted in significant survival benefit for patients with MM. In particular, our improved understanding of the BM and immune microenvironment has led to the development of highly effective immunotherapies that have demonstrated unprecedented response rates even in the multiple refractory disease setting. However, MM remains challenging to treat especially in a high-risk setting. A key mediator of therapeutic resistance in MM is the bone marrow (BM) microenvironment; a deeper understanding is necessary to facilitate the development of therapies that target MM in the context of the BM milieu to elicit deeper and more durable responses with the ultimate goal of long-term control or a cure of MM. In this review, we discuss our current understanding of the role the BM microenvironment plays in MM pathogenesis, with a focus on its immunosuppressive nature. We also review FDA-approved immunotherapies currently in clinical use and highlight promising immunotherapeutic approaches on the horizon. Full article
(This article belongs to the Special Issue Dawn of a New Era in the Microenvironment-Targeted Treatment for Multiple Myeloma)
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Graphical abstract

11 pages, 595 KiB  
Review
Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma
by Rikio Suzuki, Daisuke Ogiya, Yoshiaki Ogawa, Hiroshi Kawada and Kiyoshi Ando
Curr. Oncol. 2022, 29(11), 8529-8539; https://doi.org/10.3390/curroncol29110672 - 9 Nov 2022
Cited by 5 | Viewed by 2090
Abstract
The prognosis of patients with multiple myeloma (MM) has improved dramatically with the introduction of new therapeutic drugs, but the disease eventually becomes drug-resistant, following an intractable and incurable course. A myeloma niche (MM niche) develops in the bone marrow microenvironment and plays [...] Read more.
The prognosis of patients with multiple myeloma (MM) has improved dramatically with the introduction of new therapeutic drugs, but the disease eventually becomes drug-resistant, following an intractable and incurable course. A myeloma niche (MM niche) develops in the bone marrow microenvironment and plays an important role in the drug resistance mechanism of MM. In particular, adhesion between MM cells and bone marrow stromal cells mediated by adhesion molecules induces cell adhesion-mediated drug resistance (CAM-DR). Analyses of the role of mitochondria in cancer cells, including MM cells, has revealed that the mechanism leading to drug resistance involves exchange of mitochondria between cells (mitochondrial transfer) via tunneling nanotubes (TNTs) within the MM niche. Here, we describe the discovery of these drug resistance mechanisms and the identification of promising therapeutic agents primarily targeting CAM-DR, mitochondrial transfer, and TNTs. Full article
(This article belongs to the Special Issue Dawn of a New Era in the Microenvironment-Targeted Treatment for Multiple Myeloma)
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