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Molecular Insights into Heredity and Metabolism of Osteosarcoma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 385

Special Issue Editors


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Guest Editor
Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Nara, Japan
Interests: cancer metabolism; cachexia

E-Mail Website
Guest Editor
Department of Orthopedic Oncology and Regenerative Medicine, Nara Medical University, Kashihara, Japan
Interests: sarcoma; bone and soft tissue tumor; musculoskeletal oncology

Special Issue Information

Dear Colleagues,

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, characterized by aggressive local growth and a high propensity for metastasis. Despite advances in multimodal therapy, long-term survival remains limited, and little progress has been achieved in the past decades. Increasing evidence indicates that the biological heterogeneity of osteosarcoma arises not only from genetic alterations but also from metabolic rewiring that enables tumor adaptation to hypoxia, nutrient stress, and therapeutic pressure. The interplay between heredity and metabolism has thus emerged as a critical frontier in understanding tumor initiation, progression, and treatment resistance in osteosarcoma.

This Special Issue, Molecular Insights into Heredity and Metabolism of Osteosarcoma, aims to highlight novel discoveries at the interface of genetics and metabolism. We welcome contributions that explore inherited predispositions, somatic mutations, epigenetic regulation, and metabolic remodeling, as well as their implications for tumor biology and therapeutic strategies. By integrating molecular pathology, preclinical models, and translational approaches, this collection seeks to provide a comprehensive view of how genetic and metabolic factors shape osteosarcoma. Ultimately, our goal is to foster interdisciplinary dialogue and inspire innovative approaches that can improve outcomes for patients facing this devastating disease.

Prof. Dr. Hiroki Kuniyasu
Prof. Dr. Kanya Honoki
Guest Editors

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Keywords

  • osteosarcoma
  • clinical imaging
  • genetics
  • epigenetics
  • metabolism
  • signal transduction
  • stemness
  • pathology
  • metastasis
  • novel druggable target

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Published Papers (1 paper)

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Research

18 pages, 3189 KB  
Article
Creatine Kinase Blockade Disrupts Energy Metabolism and Redox Homeostasis to Suppress Osteosarcoma Progression
by Shingo Kishi, Rika Sasaki, Rina Fujiwara-Tani, Hitoshi Ohmori, Yi Luo, Kiyomu Fujii, Takamitsu Sasaki, Kei Goto, Yoshihiro Miyagawa, Isao Kawahara, Ryoichi Nishida, Shota Nukaga, Yukiko Nishiguchi, Ruiko Ogata, Kanya Honoki and Hiroki Kuniyasu
Int. J. Mol. Sci. 2025, 26(23), 11555; https://doi.org/10.3390/ijms262311555 - 28 Nov 2025
Viewed by 295
Abstract
Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults; yet survival outcomes have remained stagnated for decades, underscoring the urgent need for new therapeutic strategies. Creatine kinase (CK)—comprising cytosolic CKB and mitochondrial CK—maintains malignant behaviors by supporting high-energy [...] Read more.
Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults; yet survival outcomes have remained stagnated for decades, underscoring the urgent need for new therapeutic strategies. Creatine kinase (CK)—comprising cytosolic CKB and mitochondrial CK—maintains malignant behaviors by supporting high-energy phosphate transfer through the phosphocreatine (pCr) shuttle. Here, we pharmacologically inhibited CK activity in osteosarcoma models and evaluated proliferation, cell death modalities, mitochondrial function, stemness, motility, and tumor behavior. CK blockade consistently suppressed growth and clonogenicity and induced apoptosis as the predominant mode of death. It impaired ATP buffering capacity and disturbed mitochondrial homeostasis, accompanied by reduced expression of stemness-associated markers and diminished migration and invasion. In mouse models, CK inhibition significantly restrained tumor progression and dissemination. These results indicate that disabling the CK-pCr energy-buffering system reprograms cellular energetics toward apoptosis and less aggressive phenotypes. Our findings support targeting the CK pathway as a tractable metabolic vulnerability and a rational partner for cytotoxic regimens, with pathway-specific signaling alterations representing downstream consequences of central energetic collapse. Full article
(This article belongs to the Special Issue Molecular Insights into Heredity and Metabolism of Osteosarcoma)
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