Multiple myeloma

Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 27, 2024

Language: Английский

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Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

Language: Английский

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Opinion: more mouse models and more translation needed for ALS

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: May 4, 2023

Amyotrophic lateral sclerosis is a complex disorder most of which 'sporadic' unknown origin but approximately 10% familial, arising from single mutations in any more than 30 genes. Thus, there are familial ALS subtypes, with different, often unknown, molecular pathologies leading to constellation clinical phenotypes. We have mouse models for many genetic forms the disorder, these do not, on their own, necessarily show us key pathological pathways at work human patients. To date, we no 90% that 'sporadic'. Potential therapies been developed mainly using limited set models, and through lack alternatives, past tested patients regardless aetiology. Cancer researchers undertaken therapy development similar challenges; they responded by producing transformed understanding processes, implemented patient stratification multi-centre trials, effective translation basic research findings clinic. successfully adopted this combined approach, now increase our disease pathologies, rate progress moving mechanism need more, innovative, address specific questions.

Language: Английский

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Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e008979 - e008979

Published: Jan. 1, 2025

Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts efficacy of ICB therapy. Therefore, investigating how TME components in MM influence treatment is urgent.

Language: Английский

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Immune status and selection of patients for immunotherapy in myeloma: a Proposal

Blood Advances, Journal Year: 2024, Volume and Issue: 8(10), P. 2424 - 2432

Published: April 2, 2024

Abstract Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen receptor T cells or bispecific antibodies are transforming the clinical management multiple myeloma (MM). Contributions immune system to antitumor effects therapies also increasingly appreciated. Clinical malignancy in MM originates setting systemic alterations that begin early myelomagenesis regional changes affected by spatial contexture. Preexisting therapy-induced correlate with outcomes patients including after therapies. Here, we discuss insights from limitations available data about status MM. variation is emerging a major determinant efficacy current well vaccines. However, multifocal malignancy. As solid tumors, integrating aspects tumor consideration targets biology may be critical optimizing application therapy, T-cell redirection, We propose 5 distinct types provide an initial framework for optimal specific MM: depleted, permissive, excluded, suppressed, resistant. Such considerations help optimize rational patient selection improve outcomes.

Language: Английский

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Molecular and immunological mechanisms of clonal evolution in multiple myeloma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 6, 2023

Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells in bone marrow (BM). It known that early genetic mutations post-germinal center B/plasma are cause myelomagenesis. The acquisition additional chromosomal abnormalities and distinct further promote outgrowth malignant cell populations resistant to conventional treatments, finally resulting relapsed therapy-refractory terminal stages MM. In addition, supported autocrine signaling pathways tumor microenvironment (TME), which consists diverse types such as stromal cells, immune components extracellular matrix. TME provides essential signals stimuli induce and/or prevent apoptosis. particular, molecular MM interact with crucial for development To generate successful therapies recurrence, thorough understanding mechanisms drive progression therapy resistance essential. this review, we summarize key myelomagenesis expansion course cascades, well direct indirect interactions between cells. highlight drug-resistance emerging currently tested clinical trials overcome stages.

Language: Английский

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Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 20, 2023

Abstract Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of cell diversity may be key to understanding the success immunomodulatory drugs and failure PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA receptor sequencing characterize bone marrow from healthy adults ( n = 4) patients with precursor 8) full-blown MM 10). Large clones expressed immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting + LAG3 or TIGIT partially restored their function mice MM. We identify phenotypic hallmarks large intratumoral clones, demonstrate that CD27 − ratio, measured flow cytometry, serve surrogate clonal expansions an independent prognostic factor 543 treated lenalidomide-based treatment combinations.

Language: Английский

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Immune-Pathogenesis of Myeloma

Hematology/Oncology Clinics of North America, Journal Year: 2024, Volume and Issue: 38(2), P. 281 - 291

Published: Jan. 8, 2024

Language: Английский

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How to optimize the immune checkpoint blockade therapy for cancers?

ONCOLOGIE, Journal Year: 2024, Volume and Issue: 26(3), P. 343 - 348

Published: March 16, 2024

Abstract The realm of cancer therapy has been profoundly altered with the emergence immune checkpoint blockade (ICB) therapy, providing improved survival prospects for many patients some cancers. However, challenge achieving efficient or sustained therapeutic benefits underscores critical imperative to optimize ICB strategies. This review elucidates pivotal role predictive biomarkers in optimizing precision deciphering intricate dynamics associated response heterogeneity. Furthermore, it critically examines application nanotechnology-driven drug delivery as a promising avenue amplify efficacy, facilitating controlled and targeted release. Recognizing comprehensive dynamic interplay among tumor cells, stromal cells catalyzed transformative advances reverse translational research. approach enables researchers gain insights into underlying mechanisms responses, resistance mechanisms. convergence biomarkers, revolutionary nanotechnology, research emerges an indispensable focal point, propelling frontiers oncology within complex landscape therapy.

Language: Английский

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