Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июль 10, 2023

Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management OS. There been an urgent need identify new biomarkers develop specific targeted therapies. Recently, continued advancements genomic analysis have contributed identification clinically significant molecular diagnosing OS, acting as therapeutic targets, predicting prognosis. Additionally, contemporary classifications revealed that signaling pathways, including Wnt/β-catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD-1/PD-L1, MAPK, NF-κB, integral role onset, progression, metastasis, treatment response. These biological markers created avenues more accurate diagnosis relevant treatment. We herein present review recent findings modulatory pathways possible targets This also discusses current approaches, pathway-based therapies developed over past decade. covers involved curative effects traditional Chinese medicines context expression regulation genes proteins through inhibit cell growth. expected provide directions integrating genomic, molecular, profiles enhance

Язык: Английский

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Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(5), С. 189171 - 189171

Опубликована: Авг. 9, 2024

Язык: Английский

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Osteosarcoma in a ceRNET perspective

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Июнь 5, 2024

Abstract Osteosarcoma (OS) is the most prevalent and fatal type of bone tumor. It characterized by great heterogeneity genomic aberrations, mutated genes, cell types contribution, making therapy patients management particularly challenging. A unifying picture molecular mechanisms underlying disease could help to transform those challenges into opportunities. This review deeply explores occurrence in OS large-scale RNA regulatory networks, denominated “competing endogenous network” (ceRNET), wherein different biotypes, such as long non-coding RNAs, circular RNAs mRNAs can functionally interact each other competitively binding shared microRNAs. Here, we discuss how unbalancing any network component derail entire circuit, driving onset progression impacting on proliferation, migration, invasion, tumor growth metastasis, even chemotherapeutic resistance, distilled from many studies. Intriguingly, aberrant expression networks components cells be triggered also surroundings, through cytokines vesicles, with their bioactive cargo proteins highlighting relevance microenvironment. comprehensive pave way for development innovative RNA-targeted RNA-based therapies new diagnostic tools, perspective precision oncology.

Язык: Английский

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Research progress on N6-methyladenosine RNA modification in osteosarcoma: functions, mechanisms, and potential clinical applications

Medical Oncology, Год журнала: 2025, Номер 42(3)

Опубликована: Янв. 24, 2025

Язык: Английский

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Comprehensive analysis of ESCRT transcriptome-associated signatures and identification of the regulatory role of LMO7-AS1 in osteosarcoma

Cancer Cell International, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 30, 2025

Osteosarcoma (OS) is a commonly observed malignant tumor in orthopedics that has very poor prognosis. The endosomal sorting complex required for transport (ESCRT) important the development and progression of cancer may be significant target therapy. First, we built prognostic signature using 7 ESCRT-related genes (ERGs) to predict OS patient Analysis internal external datasets revealed ERG good predictive ability reproducibility. Immune analysis demonstrated correlation between immune status score. Moreover, score was found associated with response patients immunotherapy anticancer drugs. Additionally, constructed consisting 10 long noncoding RNAs (ERLs) effectively predicted prognosis patients. Furthermore, two subgroups distinct prognoses (clusters 1 2) were identified. Finally, LMO7-AS1 chosen functional experimental validation. knockdown suppressed cells. transcriptome sequencing performed on cells PI3K-Akt signaling pathway. In conclusion, our ESCRT transcriptome-associated signatures can act as biomarkers OS, novel therapeutic treatment OS.

Язык: Английский

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NF-κB signaling and the tumor microenvironment in osteosarcoma: implications for immune evasion and therapeutic resistance

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Osteosarcoma, a highly aggressive malignancy with generally poor prognosis, is characterized by tumor cells’ ability to evade immune responses and resist treatment. The nuclear transcription factor NF-κB signaling pathway crucial in regulating inflammatory reactions. It occupies central position the development of osteosarcoma microenvironment. This research aimed explore how influences recruitment polarization tumor-associated macrophages myeloid-derived suppressor cells, both which contribute immunosuppression. Furthermore, facilitates surveillance evasion cells altering expression checkpoint molecules, such as PD-L1. also enhances cell resistance chemotherapy radiotherapy activating anti-apoptotic pathways exacerbating treatment-induced inflammation. Potential therapeutic approaches include using inhibitors, possibly combination overcome mechanisms reshape antitumor responses. A thorough examination NF-κB’s role expected yield novel clinical treatment strategies, significantly improve patient prognosis targeting this key pathway.

Язык: Английский

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7-Geranyloxycoumarin modulated metastatic potential of osteosarcoma cells via interaction with MMPs and JAK1/2

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Язык: Английский

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Identifying KDM5B as the synthetic lethal target of KMT2D-mutated osteosarcoma

Chemico-Biological Interactions, Год журнала: 2025, Номер 412, С. 111451 - 111451

Опубликована: Март 6, 2025

Язык: Английский

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The Role of Epithelial–Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy

Diagnostics, Год журнала: 2025, Номер 15(5), С. 644 - 644

Опубликована: Март 6, 2025

Osteosarcoma (OS) is the most common primary malignant bone tumor, predominantly affecting children, adolescents, and young adults. Epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their cell-cell adhesion gain migratory invasive properties, has been extensively studied various carcinomas. However, its role mesenchymal tumors like osteosarcoma remains less explored. EMT increasingly recognized as key factor progression of osteosarcoma, contributing to tumor invasion, metastasis, resistance chemotherapy. This narrative review aims provide comprehensive overview molecular mechanisms driving highlighting involvement signaling pathways such TGF-β, transcription factors Snail, Twist, Zeb, microRNAs modulating EMT. Furthermore, we discuss how correlates with poor prognosis therapy patients, emphasizing potential targeting for therapeutic intervention. Recent advancements understanding have opened new avenues treatment, including inhibitors combination therapies aimed at overcoming drug resistance. By integrating biological insights clinical implications, this underscores importance critical target.

Язык: Английский

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Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 520 - 520

Опубликована: Апрель 3, 2025

Osteosarcoma is recognized as the most prevalent primary bone malignancy, primarily affecting children and adolescents. It characterized by its aggressive behavior high metastatic potential, which often leads to poor patient outcomes. Despite advancements in surgical techniques chemotherapy regimens, prognosis for patients with osteosarcoma remains unsatisfactory, survival rates plateauing over past few decades. A significant barrier effective treatment development of resistance, complicates management disease contributes recurrence. This review article aims provide a comprehensive overview recent therapy, particularly overcoming resistance. We begin discussing current standard modalities, including resection conventional agents such methotrexate, doxorubicin, cisplatin. While these approaches have been foundational managing osteosarcoma, they are limited adverse effects variability efficacy among patients. To address challenges, we explore novel pharmacological strategies that aim enhance includes targeted therapies focusing on specific molecular alterations cells immunotherapeutic designed harness body’s immune system against tumors. Additionally, innovative drug delivery systems improve bioavailability existing treatments while minimizing toxicity. The also assesses mechanisms underlying efflux mechanisms, altered metabolism, enhanced DNA repair pathways. By synthesizing research findings, highlight potential new therapeutic resistance mechanisms. Ultimately, this seeks inform future directions clinical practices, underscoring need continued innovation treating outcomes rates.

Язык: Английский

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