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Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Osteosarcoma. Core disease mechanisms, molecular and cellular pathways, in...

2026-05-08
Asta MONDO:0009807 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Osteosarcoma. Core disease mechanisms, molecular and cellular pathways, in...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Molecular Alterations Associated with Osteosarcoma Development

  • Authors: K. Ando, Kanji Mori, F. Verrecchia, B. Marc, F. Redini et al.
  • Year: 2012
  • Venue: Sarcoma
  • URL: https://www.semanticscholar.org/paper/b76a3cc461126c0c00bea324f2db2f8fed2b6e44
  • DOI: 10.1155/2012/523432
  • PMID: 22448123
  • PMCID: 3289857
  • Citations: 32
  • Influential citations: 1
  • Summary: The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.
  • Evidence snippets:
  • Snippet 1 (score: 0.582) > Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.

[2] Three‐Dimensional Osteosarcoma Models for Advancing Drug Discovery and Development

  • Authors: Cátia F. Monteiro, C. Custódio, J. Mano
  • Year: 2018
  • Venue: Advanced Therapeutics
  • URL: https://www.semanticscholar.org/paper/61c3479cbd4f975eea03b326fcbb1d60db9d5c1f
  • DOI: 10.1002/adtp.201800108
  • Citations: 26
  • Influential citations: 2
  • Summary: This review focuses on the most recent advances in 3D in vitro osteosarcoma models, highlighting the crucial role of the extracellular matrix and stromal cells in tumor progression, how they contribute to drug resistance and disease prevalence, and the future pathways toward an effective and personalized model for drug screening and validation.
  • Evidence snippets:
  • Snippet 1 (score: 0.559) > Cancer is a complex disease characterized by genetic disorders that are involved in abnormal cell growth and heterogeneous pathophysiology. Osteosarcoma (OS), a rare primary malignant disease, is the most common type of bone cancer that mainly affects children and adolescents, being also found with frequency in adults over 40. [1] Primary OS mainly arise in the long bones of the extremities, with higher incidence in the distal femur, proximal tibia, and proximal humerus. [2] This tumor commonly occurs in the metaphysis, named growth plate of the long bones where the most proliferative cells are located, and preferentially metastasize to the lung both at an initial and later stage. [3,4] OS origin is attributed to several epigenetic and/or genetic alterations in mesenchymal stem cells (MSCs) or MSC-derived osteogenic lineages, such as mutation of p53 and retinoblastoma tumor suppressor gene inactivation, under the influence of specific bone microenvironment signals. The accumulation of these DOI: 10.1002/adtp.201800108 alterations leads to the emergence of cancer stem cells (CSCs) subpopulations with selfrenewal and differentiation capacity, MSC markers expression and increased DNA repair ability, sustaining tumor growth, recurrence, metastasis and drug resistance. [5] The available therapies for OS include neoadjuvant chemotherapy with standard cytotoxic drugs such as doxorubicin, methotrexate, and cisplatin, followed by surgical resection of the primary tumor and adjuvant chemotherapy. [6] Based on National Cancer Database Report 1985-2003, these therapies are not effective, yielding a 5-year survival rate of 53.9% and besides that, patients with metastatic or recurrent disease have an extremely low survival rate (<30%). [7,8] The most critical issue that underlies these values is chemoresistance, for which the understanding of the molecular mechanisms in cancer may produce better clinical outcomes. [3] Nonetheless, the discovery of new anticancer drugs and effective therapies for OS is an emergency. The low OS prevalence

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

  • Authors: Mahmoud Zhra, S. Akhund, K. S. Mohammad
  • Year: 2025
  • Venue: Pharmaceuticals
  • URL: https://www.semanticscholar.org/paper/58fd3913b9d9892b2836686a120efcc276513ae7
  • DOI: 10.3390/ph18040520
  • PMID: 40283955
  • PMCID: 12030420
  • Citations: 19
  • Summary: The need for continued innovation in treating osteosarcoma to improve patient outcomes and survival rates is underscored, with a comprehensive overview of recent advancements in osteosarcoma therapy, particularly in overcoming chemotherapy resistance.
  • Evidence snippets:
  • Snippet 1 (score: 0.546) > Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, characterized by high metastatic potential and poor prognosis for metastatic cases [16,51]. Standard treatment for osteosarcoma typically includes a combination of surgical intervention and multi-agent chemotherapy. The surgical approach focuses on removing the tumor with adequate margins while maintaining the functionality of the affected limb [12,52]. Pre-operative and post-operative chemotherapy regimens, which include methotrexate, doxorubicin, and cisplatin (MAP), are designed to reduce tumor size before surgery and to eliminate any residual tumor cells afterward [53]. > However, systemic chemotherapy for OS faces significant challenges due to its invasive nature and the pain it causes, which can significantly impact the quality of life of patients [54]. One major issue is that systemic drugs often struggle to reach cancer cells located far from blood vessels, resulting in low drug concentrations in the affected bone. This problem is exacerbated by factors such as drug instability in the bloodstream, protein binding, and clearance by liver cells, which all contribute to toxicity related to the doses given [55]. As a result, high systemic doses are frequently required, which can lead to severe adverse effects, including myelosuppression, hepatotoxicity, cardiotoxicity, and potentially fatal central nervous system complications. Chemotherapy resistance in OS remains a significant obstacle, with over 30% of patients exhibiting resistance to current treatments or experiencing severe side effects, ultimately leading to disease progression and increased mortality [56]. To address these challenges, recent studies have concentrated on developing advanced drug delivery systems aimed at enhancing the effectiveness of chemotherapy while minimizing side effects [57]. Additionally, understanding the mechanisms of chemotherapy resistance is essential for creating new therapeutic strategies to improve patient outcomes.

[4] PERK-mediated Autophagy in Osteosarcoma Cells Resists ER Stress-induced Cell Apoptosis

  • Authors: Guang Ji, Nai-chun Yu, Xiang Xue, Zong-guang Li
  • Year: 2015
  • Venue: International Journal of Biological Sciences
  • URL: https://www.semanticscholar.org/paper/99fd43e1347182a3e65102813a6774de48937a4c
  • DOI: 10.7150/ijbs.11100
  • PMID: 26078722
  • PMCID: 4466461
  • Citations: 38
  • Influential citations: 1
  • Summary: This study implicates PERK-mediated autophagy as a significant contributor to apoptosis resistance due to ER stress in osteosarcoma cells, and implicates it as a novel target for improving osteosARcoma therapy.
  • Evidence snippets:
  • Snippet 1 (score: 0.545) > Osteosarcoma (OS) is a type of bone tumor in which the proliferating spindle cells produce osteoid or immature bone. OS accounts for 2.4 % of all malignancies in pediatric patients and about 20 % of primary bone cancers [1,2]. OS occurs mainly in the metaphysis of long bones around the knee region of the distal femur or proximal tibia. It is highly aggressive and metastasizes mainly to the lung [3]. Recently, advances in clinical treatment have helped much to improve limb salvage and reduce metastases. And multiagent dose-intensive chemotherapy methods have increased the disease-free survival rates in patients with localized disease [4]. However, frequent acquisition of drug-resistant phenotypes is often found in OS chemotherapy. It becomes a significant obstacle to develop better OS clinical treatment. With drug treatment, osteosarcoma cells activate several intracellular protective mechanisms to escape from cell death [5,6]. Earlier reports have been indicated that some strategies are used by osteosarcoma cells to obtain apoptosis resistance, such as PI3K/AKT, MDR-I and survivin pathways [7][8][9][10]. Although much progress has been made, it is still urgent to clarify molecular mechanisms underlying OS chemoresistance for clinical therapy. > In mammalian cells, many mechanisms that modulate cell homeostasis developed to maintain the balance of self construction and destruction. And one of these mechanisms is autophagy [11]. Autophagy is a fundamental lysosomal process that participates in stress tolerance. By autophagy, impaired/disrupted proteins and organelles are recruited to autophagosomes and subsequently degraded by enzymes. It is because of autophagy that intracellular components may be recycled to maintain homeostasis and prevent the accumulation of damaged cell fragements [12].

[5] Novel Therapeutic Savior for Osteosarcoma: The Endorsement of Ferroptosis

  • Authors: Cheng Qiu, Tianyi Liu, Dan Luo, D. Luan, Lin Cheng et al.
  • Year: 2022
  • Venue: Frontiers in Oncology
  • URL: https://www.semanticscholar.org/paper/7a6506ef266b707b0015d72bd11a9d196b7bf147
  • DOI: 10.3389/fonc.2022.746030
  • PMID: 35402247
  • PMCID: 8987436
  • Citations: 29
  • Summary: Four primary regulators involved in ferroptosis are outlined in this article and several critical issues are highlighted to point out future research possibilities.
  • Evidence snippets:
  • Snippet 1 (score: 0.542) > Osteosarcoma is the most common primary malignant osseous tumor accounting for the largest proportion (60%) of orthopedic malignant tumors that commonly affect children and those younger than 20 years (1,2). Distal femur and proximal tibia are the most common sites of osteosarcoma burst. However, the pathogenesis of osteosarcoma remains unclear, and it is considered to be related to the combination of genetic susceptibility, virus infection, ionizing radiation, and chemical toxins (3). Clinically, the main manifestations are swelling, pain, and dysfunction of adjacent joints, which can aggravate pain and affect patients' sleep at night (4). Several studies demonstrate that 80% of patients with osteosarcoma have a local invasion or distant metastasis when diagnosed (5). The lung is the most common organ for tumor metastasis, accounting for 85% of cases, and 90% of patients with tumors die because of metastasis (6). Current therapeutic strategies for osteosarcoma include surgical resection, radiotherapy, chemotherapy, and immunotherapy with a five-year survival rate of 70% (7). The prognosis of osteosarcoma is still unoptimistic. Tumor cells are resistant to chemotherapeutic drugs. Drug resistance is a critical factor contributing to therapeutic failure and tumor recurrence. Therefore, extensive research on elucidating the mechanisms involved in osteosarcoma and identifying relative molecular targets as well as treatment methods is warranted. > Cell death is a fundamental biological process that pervasively takes place in all living organisms (8). Cancer cells evade quintessential immune surveillance-mediated cell death and then, due to overwhelming proliferation, eventually cause dysregulation in the body (9). The five widely accepted forms of cell death are necrosis, apoptosis, necroptosis, pyroptosis, and ferroptosis (8). Pressing engagement of unknown stimulation or toxic factors concerning the unit of life could trigger uncontrolled necrosis. Additional aforementioned types are accordingly ascribed to regulated cell death (RCD) (10).

[6] Identification of Gene as Predictive Biomarkers for the Occurrence and Recurrence of Osteosarcoma

  • Authors: Yuanguo Luo, Bo Lv, Shao-Ya He, Kai-fang Zou, Kezhi Hu
  • Year: 2021
  • Venue: International Journal of General Medicine
  • URL: https://www.semanticscholar.org/paper/2c176c693a7c18860d3d415bdda2d6406ee1b573
  • DOI: 10.2147/IJGM.S312277
  • PMID: 33994806
  • PMCID: 8113014
  • Citations: 2
  • Summary: The Cox model results confirmed that the signals of ATF5, CHCHD8, and LOC286367 were robust, and it may be used in the diagnosis, treatment, and prognosis of osteosarcoma.
  • Evidence snippets:
  • Snippet 1 (score: 0.538) > International Journal of General Medicine 2021:14 WGCNA is a systems biology approach that describes correlation patterns between genes in transcriptome samples with soft threshold algorithms. 23 The results of GO and KEGG pathway enrichment analysis of the module genes led us to focus on the biological functions of autophagy and macrophage migration, as well as the HIF-1 signaling pathway and PI3K-Akt signaling pathway. Autophagy promotes the proliferation and development of osteosarcoma cells and resists tumor treatment. 30 utophagy may be involved in drug sensitivity or chemoresistance during osteosarcoma treatment. 31 acrophages are an important immune component in the osteosarcoma microenvironment. Macrophages are highly plastic and the inflammatory phenotype (M1) and antiinflammatory phenotype (M2) may play opposite roles in the progression of osteosarcoma. 32 Activation of the HIF-1 signaling pathway promotes osteosarcoma cell growth and is a promising therapeutic target. 33 Accumulating evidence suggests that the PI3K/Akt pathway is involved in cancer initiation and progression, such as tumorigenesis, apoptosis inhibition, proliferation and drug resistance. 34 o further identify the underlying molecular mechanisms of osteosarcoma recurrence, we performed enrichment analysis of the differentially expressed genes between recurrence and non-recurrence. We found multiple immune related pathways, neutrophil mediated immunity, neutrophil apoptotic process, and leukocyte homeostasis. They may be associated with metastasis and recurrence of osteosarcoma. 35 In addition to a large number of aberrant biological functions, FOXO could control the expression of genes involved in cell death and cell cycle arrest, exerting tumor suppressor activity. 36 Tumor suppressor p53 tumor cells have been reported to exert anticancer effects by inducing cell cycle arrest and apoptosis. 37 f the 13 coexpression modules we identified, module 1 was found to be strongly associated with osteosarcoma.

[7] Interfering with UBE2L3 expression targets regulation of MLKL to promote necroptosis inhibition of growth in osteosarcoma

  • Authors: Xiwu Zhao, Guoqiang Shan, Deguo Xing, Hongwei Gao, Zhenggang Xiong et al.
  • Year: 2025
  • Venue: World Journal of Surgical Oncology
  • URL: https://www.semanticscholar.org/paper/b34edeb4263d09ee26ffa4556fc2d310f13a0c11
  • DOI: 10.1186/s12957-025-03715-3
  • PMID: 39988669
  • PMCID: 11849225
  • Citations: 1
  • Summary: Investigating the molecular mechanisms by which interfering with UBE2L3 expression promotes necroptosis and impacts the progression of osteosarcoma suggests that inhibiting the expression of UBE2L3 can suppress the growth of osteosarcoma.
  • Evidence snippets:
  • Snippet 1 (score: 0.532) > Osteosarcoma is a rare but serious malignant tumor that primarily occurs in the growth areas of bones and soft tissues. According to recent epidemiological data, approximately 1-2 per million people are diagnosed with osteosarcoma worldwide, with a higher prevalence among children and adolescents aged 10-25 years [1]. The incidence rate of osteosarcoma is slightly higher in males than females, with a male-to-female ratio of approximately 1.4:1 [2,3]. The aggressive nature and high susceptibility to metastasis are among the defining characteristics and major clinical challenges of osteosarcoma. If left untreated, osteosarcoma can cause localized pain, swelling, and pathological fractures due to tumorinduced bone destruction. As the disease progresses, tumor cells primarily metastasize to the lungs through the bloodstream, while lymph node and other bone metastases are less common. This propensity for distant metastasis, particularly to the lungs, contributes to the high lethality of osteosarcoma, with a 5-year survival rate of approximately 20-30% for metastatic disease [4,5]. > The pathogenesis of osteosarcoma is associated with necroptosis, a form of regulated cell death mediated by RIPK1, RIPK3, and MLKL. Necroptosis is distinct from apoptosis, as it involves the loss of cell membrane integrity and the release of cellular contents, often triggering inflammatory responses [6,7]. Recent studies suggest that osteosarcoma cells may undergo necroptosis under specific conditions when exposed to chemotherapy drugs or radiation therapy, primarily due to the accumulation of reactive oxygen species (ROS) and DNA damage [8,9]. Dysregulated activation of pathways such as p53 may also indirectly influence necroptosis by modulating oxidative stress responses [10,11]. Given the involvement of multiple signaling pathways in necroptosis regulation, further exploration of its molecular mechanisms in osteosarcoma may lead to innovative therapeutic strategies, enhancing the efficacy of conventional treatments and improving patient outcomes. MLKL is a key execution protein in the necroptosis pathway, playing a central role in cell death signal transduction.

[8] Identification of Key Genes and miRNAs Affecting Osteosarcoma Based on Bioinformatics

  • Authors: Le Li, Xiaoxia Zhou, Wencan Zhang, Ran Zhao
  • Year: 2022
  • Venue: Disease Markers
  • URL: https://www.semanticscholar.org/paper/ddde566df49e94e4df8fce9703cdf737d060bd5d
  • DOI: 10.1155/2022/1015593
  • PMID: 36438897
  • PMCID: 9683959
  • Citations: 1
  • Summary: The enrichment analysis showed that the common DEGs of GSE70367 and GSE69470 were related with cell development, covalent chromatin modification, and histone modification and involve in the regulation of MAPK, mTOR, and AMPK pathways.
  • Evidence snippets:
  • Snippet 1 (score: 0.526) > Osteosarcoma is a frequent malignant bone disease in children and older patients, which is characterized with poor prognosis including physical disability and metastases [1,2]. Surgery excision, radiotherapy, and chemotherapy have been widely used for osteosarcoma treatment, which can effectively inhibit the development of the tumor progression in the early stage [3]. Nevertheless, considerable patients have been confirmed to be at the advanced stage in their first clinical diagnosis. Moreover, high metastasis rates of osteosarcoma also make the clinical intervention become tricky and then lead to treatment failure [4]. Although the survival times of the patients have been significantly prolonged with the modern medicine techniques, the treatment effect remains unsatisfactory for patients [5,6]. At present, some reports have focused on revealing the potential mechanism of osteosarcoma, which can provide valuable reference for the progression of medicine strategies [7,8]. At present, there have been many studies on the molecular mechanism of osteosarcoma, and several osteosarcoma-driving genes have been identified, such as TP53, RB1, and PTEN. There have also been targeted drugs for osteosarcoma, such as pazopanib, appatinib, cabotinib, and ivermex. However, these studies have not clearly explained the pathogenesis and metastasis of osteosarcoma. Therefore, it is urgent to further study the potential molecular mechanism of osteosarcoma cells, identify reliable molecular markers, and identify new drug targets. > Microarray analysis is a useful method which has been used for screening the key genes in diseases [9]. Recently, the academic and guiding value of bioinformatics methods on improving the clinical practice have been proven by numerous researches [10]. MicroRNA is a class of the short noncoding RNA with 18-20 nucleotides, which plays a great part in the cellular life activity [11]. The abnormal expression of miRNA is a biomarker event in multiple diseases, especially in caner. In osteosarcoma, many studies have indicated that miRNA can regulate the cellular phenotype to influence the progression of the tumor via intervening the expression of key proteins [12].

[9] Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma

  • Authors: A. Shaikh, Fangfei Li, Min Li, Bing He, Xiaojuan He et al.
  • Year: 2016
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/b4b6c41cef2d5ecf6f28565228bbab80daf1445e
  • DOI: 10.3390/ijms17040506
  • PMID: 27058531
  • PMCID: 4848962
  • Citations: 121
  • Summary: This review summarizes the current development of molecular mechanisms and targets for osteosarcoma and Therapies that target these mechanisms with updated information on clinical trials are reviewed.
  • Evidence snippets:
  • Snippet 1 (score: 0.515) > Osteosarcoma (OS) is a primary bone cancer, predominantly affecting children and adolescence population [1]. OS originates from primitive mesenchymal bone forming cells and often occurs in long bones, such as proximal tibia and distal femur [2,3]. Current OS treatment regime consists of the combination of surgery and intensive multi-agent chemotherapy. Ever since the introduction of chemotherapy, five-year survival rate among OS patients has improved to 60%-75% [4]. However, 30%-40% of OS patients are associated with pulmonary metastasis and relapse, which have significantly poor prognosis, with an overall five-year survival rate of about 20% [5]. Moreover, over the past few decades, no substantial improvement in survival rate has been achieved, though efforts were made by intensifying dosing, varying timing and using multi-combinational chemotherapy. Additionally, several adverse effects are accompanied by high-dose chemotherapy [6]. Hence, there is an increasing sense of urgency to identify new biological markers and develop novel, innovative and specific molecular targeted therapeutic approaches to improve the outcome in osteosarcoma patients with poor prognosis. In this review, we will discuss about molecular mechanism underlying osteosarcoma, current molecular therapeutic targets against immune system, extracellular and Intercellular signaling transduction pathway of the bone metabolism, as well as novel therapeutic targets and drug delivery systems that have been investigated or are currently undergoing investigation in translational studies (Figure 1). > is an increasing sense of urgency to identify new biological markers and develop novel, innovative and specific molecular targeted therapeutic approaches to improve the outcome in osteosarcoma patients with poor prognosis. In this review, we will discuss about molecular mechanism underlying osteosarcoma, current molecular therapeutic targets against immune system, extracellular and Intercellular signaling transduction pathway of the bone metabolism, as well as novel therapeutic targets and drug delivery systems that have been investigated or are currently undergoing investigation in translational studies (Figure 1).

[10] Osteosarcoma: From Molecular Biology to Mesenchymal Stem Cells

  • Authors: M. Broadhead, Saumiyar Sivaji, Z. Balogh, P. Choong
  • Year: 2017
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/fd25c72bc7c0f5742654c8167d9cbc956afbc2d3
  • DOI: 10.5772/67371
  • Citations: 5
  • Influential citations: 1
  • Summary: This work has shown that interactions of MSCs with osteosarcoma cells in the tumour microenvironment may cause increased cell proliferation, in stark contrast to the role of M SCs as a promising source for tissue repair and regeneration.
  • Evidence snippets:
  • Snippet 1 (score: 0.510) > The pathogenesis of osteosarcoma is a complex process, which is not completely understood and involves tumorigenesis from mesenchymal cells, alterations in cellular apoptosis, adhesion, migration and invasion, as well as tumour-induced osteolysis and angiogenesis.Various genetic and molecular alterations underlie these processes.It is hoped that by targeting the deranged molecular signalling of these pathways that novel treatment agents could be developed that enhance the efficacy of conventional chemotherapeutics and possibly reduce patient morbidity.

[11] Molecular pathogenesis and therapeutic strategies of human osteosarcoma

  • Authors: S. Denduluri, Zhongliang Wang, Zhengjian Yan, Jing Wang, Q. Wei et al.
  • Year: 2015
  • Venue: Journal of Biomedical Research
  • URL: https://www.semanticscholar.org/paper/c3a438369c1d4c03e198761da58e1b294e2c3f98
  • DOI: 10.7555/JBR.30.20150075
  • PMID: 26496981
  • PMCID: 4726829
  • Citations: 42
  • Influential citations: 3
  • Summary: Current understanding of OS disease processes is summarized and light is shed on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.509) > Abstract Osteosarcoma (OS) is a devastating illness with rapid rates of dissemination and a poor overall prognosis, despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens. Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets. Defects in mesenchymal stem cell differentiation, abnormal expression of oncogenes and tumor suppressors, and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes. As such, a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies. Born out of these and similar investigations, a variety of emerging therapies are now undergoing various phases of OS clinical testing. They broadly include angiogenesis inhibitors, drugs that act on the bone microenvironment, receptor tyrosine kinase inhibitors, immune system modulators, and other radio- or chemo-sensitizing agents. As new forms of drug delivery are being developed simultaneously, the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever. In this review, we not only summarize our current understanding of OS disease processes, but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

[12] Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma

  • Authors: Yubo Xiang, Yingxin Yang, Jia Liu, Xu Yang
  • Year: 2023
  • Venue: Frontiers in Oncology
  • URL: https://www.semanticscholar.org/paper/7ee4005d3ffedc8e55a01bbc619244b5583a3a1d
  • DOI: 10.3389/fonc.2023.1219211
  • PMID: 37404761
  • PMCID: 10315918
  • Citations: 22
  • Summary: This article reviews recent research advances on the role and clinical application of PI3K/AKT pathway and miRNA/PI3K /AKT axis in the development of osteosarcoma and identifies potential biomarkers for osteosARcoma diagnosis, treatment and prognostic assessment.
  • Evidence snippets:
  • Snippet 1 (score: 0.505) > Osteosarcoma (OS) is a primary malignant bone tumor derived from bone forming mesenchymal stem cells. It is highly malignant and can be locally aggressive and often leading to pulmonary or even systemic metastases. Children and adolescents are the most common patients with osteosarcoma, second only to lymphoma and brain tumors in the childhood and adolescent population (1)(2)(3). The distal end of the femur is the most common site for osteosarcoma, followed by the proximal end of the tibia and humerus (2,(4)(5)(6). Local invasion is observed in more than 85% of osteosarcoma patients, with lung metastases being the most common in 74% of patients with metastases, followed by bone metastases in 9% of patients, and both bone and lung metastases in 8% of patients with metastases (6). In recent decades, surgery combined with new chemotherapy has been recognized as the standard treatment for osteosarcoma, significantly improving overall survival and quality of life (7). Emerging chemotherapy regimens include cisplatin (DDP), a d r i a m y c i n ( D O X ) , m e t h o t r e x a t e ( M T X ) , a n d isocyclophosphamide (IFO) (7). However, the therapeutic effect of chemotherapeutic agents is limited by various reasons, such as escape of apoptosis, reduced drug uptake, and increased drug metabolism. Systemic metastasis limits the effectiveness of surgical resection, so metastatic and drug resistance often result in unsatisfactory outcomes and prognosis for patients with osteosarcoma (8). The problems described above involve changes in multiple biological processes, including changes in genetic and epigenetic characteristics. Understanding and studying the molecular changes of genes associated with the formation of osteosarcoma and associated signaling pathways will help uncover the mechanisms underlying its occurrence and development, providing new directions for the diagnosis, targeted therapy, and prognosis of osteosarcoma.

[13] Global research trends and hotspots in metabolomics of osteosarcoma: a decade-spanning bibliometric and visualized analysis

  • Authors: Jun-Bo Tu, Tao Liu, Jun-Feng Li, Jianglan Long, Xiu Q Wang et al.
  • Year: 2024
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/b263dfc2df6e9cb7d76c55bf4fa3a27761b9a900
  • DOI: 10.3389/fimmu.2024.1463078
  • PMID: 39445018
  • PMCID: 11496093
  • Citations: 3
  • Summary: The evolution and convergence of research themes in osteosarcoma metabolomics over the past decade is delineated, major contributors are identified, and forecast emerging trends that could direct future research efforts are forecast.
  • Evidence snippets:
  • Snippet 1 (score: 0.505) > The molecular mechanisms related to osteosarcoma metabolism mainly involve signal transduction pathways, gene expression regulation, and cell proliferation and apoptosis mechanisms. Research mainly focuses on the occurrence, development and treatment response mechanisms of osteosarcoma, especially the key molecules and pathways that lead to tumor growth and metastasis. Autophagy is an important process that maintains cellular homeostasis. This process is complex and involves the removal of damaged proteins and organelles. In osteosarcoma, autophagy may play a dual role, that is, it can induce cell death and maintain the survival of tumor cells. Understanding molecular mechanisms and autophagy can provide insights into the mechanisms of cancer and can also help develop new treatment strategies. For example, the cancer-promoting protein IF1 helps tumor cell growth by promoting mitochondrial renewal and energy conservation (64). Sergio Almansa-Gomez, Francisco Prieto-Ruiz and others made a review on the regulation of autophagy in osteosarcoma. They believed that many results have been achieved in the regulation of autophagy in osteosarcoma in the past, but future research still needs to elucidate the role of autophagy. Molecular mechanisms and their relationship to osteosarcoma (65).

[14] Targeting the mammalian target of rapamycin pathway in osteosarcoma using combinative chemotherapy

  • Authors: Pei‐yi Liu, Wei-bin Zhang, Yili Wei
  • Year: 2013
  • Venue: Chinese Medical Journal
  • URL: https://www.semanticscholar.org/paper/854effcfc78c7297b3e5b92fa3221faa97a09db7
  • DOI: 10.3760/cma.j.issn.0366-6999.20112107
  • PMID: 23673121
  • Citations: 1
  • Summary: Although multiple chemotherapy regimens have improved the outcome of patients with osteosarcoma, resistance to current regimens has been reported in more than 30% of patients, highlighting the need for novel, targeted therapies.
  • Evidence snippets:
  • Snippet 1 (score: 0.500) > Osteosarcoma is a highly aggressive tumor with a higher rate of metastasis than most cancers in children and young adults. The prognosis of patients with osteosarcoma is associated with response to chemotherapy; however osteosarcoma is highly resistant to current treatment regimens. Understanding the molecular mechanisms underlying the development and malignant behavior of osteosarcoma is crucial for developing targeted therapeutic approaches and for the identification of novel chemotherapy agents.

[15] Down‐regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial–mesenchymal transition

  • Authors: Si-Ning Xing, Changdong Wang, Huying Tang, Jiaying Guo, Xing Liu et al.
  • Year: 2020
  • Venue: FEBS Open Bio
  • URL: https://www.semanticscholar.org/paper/5214c55fa1a798f04d89ee469558eb977d13c8b1
  • DOI: 10.1002/2211-5463.12915
  • PMID: 32580247
  • PMCID: 7459394
  • Citations: 13
  • Summary: It is suggested that PDGFRβ plays an important role in OS invasion, migration and epithelial–mesenchymal transition by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDG FRβ as a potential therapeutic target for OS.
  • Evidence snippets:
  • Snippet 1 (score: 0.500) > As a cancerous tumor that originates from bone, osteosarcoma (OS) is the most frequent histological type of primary bone cancer and is becoming the second leading cause of cancer-related deaths in children and adolescents [1]. It accounts for ~20% of all primary bone cancers and 2.4% of all malignancies, with high mortality and morbidity in children [2]. Tumor metastasis, especially lung metastasis, is the main reason for the death of patients with OS [3]. Approximately one-fifth of the patients have micrometastasis in the lungs when OS is diagnosed. Surgery is an important way to treat this disease, but the subsequent complications may result in more serious consequences [4]. A variety of agents have been investigated for the treatment of OS in clinical trials. Although several studies focus on the molecular mechanism of OS, the specific mechanism remains unclear. Further research on OS pathogenesis may provide new ideas for the treatment of OS. With the discovery of an increasing number of molecular mechanisms that can mediate the invasion and metastasis of OS, epithelial-mesenchymal transition (EMT) has aroused interest [5][6][7]. EMT is one of the transformations by which tumor cells can acquire the ability to migrate and is an important process in tumor cell infiltration and metastasis [8,9]. It has been reported that EMT is highly correlated with the invasive and metastatic performances of many types of tumor cells [10,11] and especially promotes the metastasis of epithelial neoplasms [12]. EMT also plays a pivotal position in primary and secondary metastases in OS [13]. > Receptor tyrosine kinases (RTKs) are key players in the regulation of numerous fundamental cellular processes, such as growth, migration and apoptosis, and are involved in tumorigenesis, disease progression and metastatic spread of numerous human cancers [14][15][16][17]. Platelet-derived growth factor receptor (PDGFR) belongs to the family of type III tyrosine protein kinases, and PDGFR beta (PDGFRβ) is an important subtype of PDGFR.

[16] Integrated gene network analysis sheds light on understanding the progression of Osteosarcoma

  • Authors: Hrituraj Dey, K. Vasudevan, G. Doss C., S. U. Kumar, A. El Allali et al.
  • Year: 2023
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/2dbcc0c2f0f8379bdf5b389aa75d140c1a1b975b
  • DOI: 10.3389/fmed.2023.1154417
  • PMID: 37081847
  • PMCID: 10110863
  • Citations: 6
  • Summary: This study aims to highlight the hub genes involved in gene-gene interaction network to understand their interaction and how they affect the various biological processes and signaling pathways involved in Osteosarcoma and highlights the candidate hub genes viz.
  • Evidence snippets:
  • Snippet 1 (score: 0.500) > A cancer cell will essentially have six hallmark capabilities to be recognized as a cancer cell. The six core hallmarks outlined by Hananah and Weinberg include self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis, along with the emerging hallmarks of cancer which includes deregulating cellular energetics and avoiding immune destruction (24, 25). Attaining each capability will likely involve inactivating or eluding a specific control mechanism. We have utilized a gene interaction network in our study to understand the development and progression of the tumor cells in Osteosarcoma. This helped us decipher a group of highly interactive genes responsible for the pathogenesis and spread of the disease. > During analysis, MF observed were kinase binding, kinase regulator activity, and transcription factor activity. Prior studies on Osteosarcoma have highlighted that protein tyrosine kinases are essential signaling molecules involved in the signaling pathways that regulate cellular differentiation and proliferation (26). The enriched BPs of Osteosarcoma included signal transduction, cell communication, regulation of cell cycle, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, apoptosis, protein metabolism, energy pathways, metabolism along with cell cycle checkpoint signaling, DNA damage checkpoint signaling, and response to hypoxia. Earlier studies have shown that impairment in signal transduction, cell communication, and cell cycle checkpoint signaling has significantly promoted Osteosarcoma (27). Signal transduction is a sequential event where an extracellular signal is transduced by the cell to create a response, which is necessary for the normal growth and development of the cell. Since genetic alterations drive cancer, these alterations create a wide range of aberrant signaling networks that drives the expansion of the tumor. These signaling pathways control tumor growth, development, and fate (28). The signal transduction pathway involved 14 genes namely CCND1, CDK4, VEGFA, CDKN2A, SRC, CHEK2, ERBB2, CD44, CCNE1, PLK1, CDC6, AURKA, CCNB2, and TNFSF11.

[17] Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

  • Authors: V. Sarhadi, Ravindra Daddali, R. Seppänen-Kaijansinkko
  • Year: 2021
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/6983a860b85ab0a97b3c53018b39acfd16a09b35
  • DOI: 10.3390/ijms222011035
  • PMID: 34681692
  • PMCID: 8537935
  • Citations: 51
  • Influential citations: 1
  • Summary: The role of MSC-EVs is highlighted, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy, to highlight the high heterogeneity and genetic complexity of OS.
  • Evidence snippets:
  • Snippet 1 (score: 0.495) > Osteosarcoma (OS) is the most predominant primary bone cancer, commonly occurring in the long bones of children and adolescents [1]. OS is highly malignant and the major complications in OS arise due to a lack of immune response, leading to irregular bone growth and distant metastases, seen commonly in the lungs and liver. The current treatment approaches for OS are preoperative chemotherapy, surgical resection, and postoperative chemotherapy, which are effective in patients with localized OS. Conversely, patients with advanced, metastatic, and recurrent OS develop resistance to chemotherapy, which makes it difficult to treat, resulting in a poor prognosis [2]. Despite multidisciplinary treatments, there has been no change in the prognosis during the past two decades. The overall 5-year survival rate of OS patients is 65% in the case of localized disease, while it is 20% in those with metastasis, and significantly lower in those with lung metastasis [3]. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets [4]. > A thorough understanding of the tumor microenvironment (TME), especially the bone microenvironment (BME), cellular crosstalk, and the molecular mechanisms underlying tumor progression, is essential for drug design and for developing new drug molecules for OS treatment. The BME is composed of the extracellular matrix (ECM) and a variety of cells, which includes mesenchymal stem cells (MSCs), endothelial cells, macrophages, stem cells, fibroblasts, osteoblasts, osteoclasts, and osteocytes that are organized to maintain the bone rigidity and the structural as well as functional integrity of the bone niche. All these cells together play a crucial role in normal bone development and bone physiology and can also lead to osteosarcoma in aberrant conditions. > MSCs are multipotent, non-hematopoietic cells that have the potential to self-rejuvenate and to differentiate into different cell types, including muscle cells, hepatocytes, osteoblasts, adipocytes, chondrocytes, and stromal cells [5,6].

[18] Involvement of TP53 in osteosarcoma - challenges and prospects

  • Authors: Yue Shen, Shuzhou Huang, Geng Chen, Guangda Wang, L. Sui
  • Year: 2025
  • Venue: Frontiers in Oncology
  • URL: https://www.semanticscholar.org/paper/f4de5949ca03e6677f6b90cc0b23d966a37a92dc
  • DOI: 10.3389/fonc.2025.1605080
  • PMID: 41323391
  • PMCID: 12657174
  • Citations: 3
  • Summary: This review provides an in-depth analysis of p53 biology in OS, highlighting its impact on therapeutic resistance and tumor progression and underscores opportunities for translational research aimed at improving the clinical outcomes of OS patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.494) > The pivotal role of p53 dysregulation in osteosarcoma pathogenesis and therapeutic resistance is now well-established. Mutant p53 proteins, particularly those with gain-of-function mutations, contribute significantly to disease progression and are present in over 50% of osteosarcoma cases. These mutations are categorized into structural and contact types based on their distinct mechanisms of disrupting p53 function, with structural mutations frequently involving non-random intronic breakpoints that may confer selective advantages during tumor evolution. The precise characterization of these genetic alterations provides not only insights into tumor biology but also critical opportunities for clinical translation. > From a diagnostic perspective, the recurrent identification of specific mutant alleles in patients experiencing sequential relapsesas well as in experimentally validated drug-resistant models-offers a strong rationale for developing mutation-specific prognostic biomarkers and targeted therapeutic strategies. These findings are particularly relevant for overcoming methotrexate resistance, a major clinical challenge in osteosarcoma management. The translation of these molecular insights into clinically applicable tools represents a promising direction for personalized treatment approaches. > Therapeutically, significant progress has been made in developing agents that target p53 pathways, including novel MDM2 inhibitors and p53-stabilizing compounds, several of which are currently in preclinical and early clinical development. Beyond conventional chemotherapy, contemporary research emphasizes combinatorial strategies that address resistance mechanisms through immunomodulation, metabolic targeting, and stem cell pathway inhibition. Emerging approaches such as mutation-specific promoter editing, enhancer reprogramming, and functional genetic screens offer additional avenues for identifying therapeutic vulnerabilities. Collectively, these advances are shaping a new paradigm of precision medicine in osteosarcoma, providing hope for improved outcomes through biologically rational and individualized treatment strategies.

[19] Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

  • Authors: Emel Rothzerg, X. D. Ho, Jiake Xu, D. Wood, A. Märtson et al.
  • Year: 2021
  • Venue: Genes
  • URL: https://www.semanticscholar.org/paper/85ee116d09d4cb8c4cbb748ce325a97bbc981099
  • DOI: 10.3390/genes12081132
  • PMID: 34440306
  • PMCID: 8394133
  • Citations: 36
  • Summary: This study investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples using RNA sequencing and identified 15 that were upregulated in tumour samples compared to bone sample controls.
  • Evidence snippets:
  • Snippet 1 (score: 0.490) > Osteosarcoma (OS), also known as osteogenic sarcoma, is the most common primary malignant solid tumour of bone [1]. The peak incidence is in children and adolescents with a smaller second peak in incidence after the age of 65 years associated with Paget's disease of bone [2]. OS commonly develops in the extremities of long bones such as the distal femur, proximal tibia, proximal humerus, and proximal femur [3]. It is an aggressive-invasion sarcoma type that frequently metastasizes to the lung and other bones in the body [4]. OS usually presents with pain, tenderness and swelling around the affected bone, and diagnosis is achieved by a combination of imaging and histology with the characteristic appearance of malignant cells forming osteoid [5]. Cytotoxic chemotherapy was introduced by Rosen in the 1970s and improved the prognosis from 20% to a 70% five-year survival rate with no further significant improvements in outcome since then [6]. Current treatments of OS include neo-adjuvant chemotherapy with drugs such as doxorubicin, methotrexate, and cisplatin with the aim of reducing tumour size as well as eradicating micro-metastases. Ablative surgery is then followed by further chemotherapy determined by the cell death rate observed in the surgical specimens [7,8]. Current OS therapeutic agents are limited to cytotoxic drugs interfering with transcription and DNA replication [6]. This is a reflection of our knowledge of the pathways involved in OS initiation and progression, which are insufficient to understand the underlying molecular mechanisms of the disease. > The sense strand of DNA provides the template for production of messenger RNA (mRNA) to be translated into proteins [9], but the Human Genome Project highlighted that only 1.5% of the human genome contains protein-coding genes. In addition, the Encyclopedia of DNA elements (ENCODE) and the Functional Annotation of the Mammalian Genome (FANTOM) have suggested that the majority of the genome is transcribed and produces a various amount of non-coding RNA species (ncRNAs) [10,11].

[20] The Molecular Pathogenesis of Osteosarcoma: A Review

  • Authors: M. Broadhead, Jonathan C. M. Clark, D. Myers, C. Dass, P. Choong
  • Year: 2011
  • Venue: Sarcoma
  • URL: https://www.semanticscholar.org/paper/9d7784947e608548778f2eeb255836884b6829ce
  • DOI: 10.1155/2011/959248
  • PMID: 21559216
  • PMCID: 3087974
  • Citations: 357
  • Influential citations: 12
  • Summary: The pathogenic mechanisms of osteosarcoma oncogenesis and progression are outlined and some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.485) > Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.