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Cells Apr 2020Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor... (Review)
Review
Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor progression and treatment responsiveness are not completely defined for these tumors, and the powerful discovery of genetic analysis is highly warranted in the view of improving the therapy and cure of patients. The review summarizes recent advances concerning the molecular and genetic background of these three neoplasms and, of their most common variants, highlights the putative therapeutic targets and the clinical trials that are presently active, and notes the fundamental issues that remain unanswered. In the era of personalized medicine, the rarity of sarcomas may not be the major obstacle, provided that each patient is studied extensively according to a road map that combines emerging genomic and functional approaches toward the selection of novel therapeutic strategies.
Topics: Bone Neoplasms; Genomics; Humans; Precision Medicine
PubMed: 32295254
DOI: 10.3390/cells9040968 -
Matrix Biology : Journal of the... 2016Metastasis is the major cause of death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms... (Review)
Review
Metastasis is the major cause of death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms underlying the metastatic process is necessary for future prevention and treatment. The tumor microenvironment is now known to play a role in the metastatic cascade, both at the primary tumor and in metastatic sites, and includes both cellular and non-cellular components. The extracellular matrix (ECM) provides structural support and signaling cues to cells. One particular group of molecules associated with the ECM, known as matricellular proteins, modulate multiple aspects of tumor biology, including growth, migration, invasion, angiogenesis and metastasis. These proteins are also important for normal function in the bone by regulating bone formation and bone resorption. Recent studies have described a link between some of these proteins and metastasis of various tumors to the bone. The aim of this review is to summarize what is currently known about matricellular protein influence on bone metastasis. Particular attention to the contribution of both tumor cells and non-malignant cells in the bone has been given.
Topics: Bone Neoplasms; Extracellular Matrix Proteins; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Tumor Microenvironment
PubMed: 26807761
DOI: 10.1016/j.matbio.2016.01.006 -
Journal of Immunology Research 2021The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint... (Review)
Review
The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.
Topics: Bone Neoplasms; Clinical Trials as Topic; Humans; Immune Checkpoint Inhibitors; Progression-Free Survival; Tumor Microenvironment
PubMed: 34877360
DOI: 10.1155/2021/8970173 -
Cancer Medicine Apr 2023Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital...
OBJECTIVE
Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression.
METHODS
In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis.
RESULTS
ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways.
CONCLUSION
Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.
Topics: Child; Young Adult; Humans; Animals; Mice; Cisplatin; Antineoplastic Agents; Drug Resistance, Neoplasm; Apoptosis; Neoplasm Recurrence, Local; Osteosarcoma; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Integrin beta3
PubMed: 36772869
DOI: 10.1002/cam4.5585 -
Nature Reviews. Endocrinology Jan 2016In the context of breast cancer, the importance of the skeleton in the regulation of primary tumour development and as a site for subsequent metastasis is well... (Review)
Review
In the context of breast cancer, the importance of the skeleton in the regulation of primary tumour development and as a site for subsequent metastasis is well characterized. Our understanding of the contributions made by the host bone and bone marrow cells increasingly demonstrates the extent of the interaction between tumour cells and normal host cells. As a result, the need to develop and utilize therapies that can impede the growth and/or function of tumour cells while sparing normal host bone and bone marrow cells is immense and expanding. The need for these new treatments is, however, superimposed on the orthopaedic management of patients' quality of life, where pain control and continued locomotion are paramount. Indeed, the majority of the anticancer therapies used to date often result in direct or indirect damage to bone. Thus, although the bone microenvironment regulates tumour cell growth in bone, cells within the bone marrow niche also mediate many of the orthopaedic consequences of tumour progression as well as resistance to the antitumour effects of existing therapies. In this Review, we highlight the effects of existing cancer treatments on bone and the bone marrow microenvironment as well as the mechanisms mediating these effects and the current utility of modern orthopaedic interventions.
Topics: Bone Marrow; Bone Neoplasms; Breast Neoplasms; Disease Management; Female; Humans; Quality of Life; Tumor Microenvironment
PubMed: 26503674
DOI: 10.1038/nrendo.2015.185 -
Clinical Orthopaedics and Related... Apr 2019
Topics: Bone Neoplasms; Congresses as Topic; Humans; Muscle Neoplasms; Treatment Outcome
PubMed: 30811356
DOI: 10.1097/CORR.0000000000000653 -
Hellenic Journal of Nuclear Medicine 2021To evaluate the clinical utility of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) for primary bone...
OBJECTIVE
To evaluate the clinical utility of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) for primary bone neoplasms.
SUBJECTS AND METHODS
Bone SPECT/CT scans of 23 patients with 19 benign bone neoplasms (5 osteoid osteomas, 4 bone giant cell tumor, 4 osteofibrous dysplasia, 3 intraosseous ganglion, 2 aneurysmal bone cyst, 1 intraosseous hemangioma) and 5 malignant bone neoplasms (2 osteosarcoma, 1 periosteal osteosarcoma, 1 malignancy in bone giant cell tumor, 1 Ewing sarcoma) were retrospectively analyzed with maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) of primary lesions.
RESULTS
Mean SUVmax of 19 benign and 5 malignant primary bone neoplasms were 6.89±3.26 (range 3.9-15.13) and 10.31±3.19 (5.0-13.45) respectively, with statistically significant difference (P=0.048). Mean SUVpeak of those were 5.87±2.83 (range 3.5-13.63) and 9.18±3.05 (4.09-12.03) respectively, with statistically significant difference (P=0.032). Mean SUVmean of those were 4.43±2.11 (range 2.59-9.37) and 7.13±2.90 (3.3-10.42) respectively, with statistically significant difference (P=0.027). Mean MBV of those were 22.0±30.0 (range 2.47-110.61) and 27.8±39.94 (8.59-99.24) respectively, with no statistically significant difference (P=0.72). Mean TBU of those were 80.64±94.57 (range 10.50-373.57) and 166.60±203.97 (28.68-528.13) respectively, with no statistically significant difference (P=0.17).
CONCLUSION
Quantitative values obtained with bone SPECT/CT may serve as osteoblastic biomarkers for primary bone neoplasm.
Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 33866337
DOI: 10.1967/s002449912304 -
Annals of Palliative Medicine Aug 2017
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Palliative Care; Periodicals as Topic
PubMed: 28866907
DOI: 10.21037/apm.2017.08.14 -
The Quarterly Journal of Nuclear... Jun 2019Bone metastases remain a common feature of advanced cancers and are associated with significant morbidity and mortality. Recent research has identified promising novel... (Review)
Review
Bone metastases remain a common feature of advanced cancers and are associated with significant morbidity and mortality. Recent research has identified promising novel treatment targets to improve current treatment strategies for bone metastatic disease. This review summarizes the well-known and recently discovered molecular biology pathways in bone that govern normal physiological remodeling or drive the pathophysiological changes observed when bone metastases are present. In the rapidly changing world of targeted cancer treatments, it is important to recognize the specific treatment effects induced in bone by these agents and the potential impact on common imaging strategies. The osteoclastic targets (bisphosphonates, LGR4, RANKL, mTOR, MET-VEGFR, cathepsin K, Src, Dock 5) and the osteoblastic targets (Wnt and endothelin) are discussed, and the emerging field of osteo-immunity is introduced as potential future therapeutic target. Finally, a summary is provided of available trial data for agents that target these pathways and that have been assessed in patients. The ultimate goal of research into novel pathways and targets involved in the tumor-bone microenvironment is to tackle one of the great remaining unmet needs in oncology, that is finding a cure for bone metastatic disease.
Topics: Animals; Bone Matrix; Bone Neoplasms; Humans; Immunity, Innate; Molecular Targeted Therapy; Osteoclasts; Tumor Microenvironment
PubMed: 31298015
DOI: 10.23736/S1824-4785.19.03203-5 -
Oncotarget Aug 2016Osteosarcoma (OS) is a common primary malignant bone tumor with high morbidity and mortality in children and young adults. How to improve poor prognosis of OS due to... (Review)
Review
Osteosarcoma (OS) is a common primary malignant bone tumor with high morbidity and mortality in children and young adults. How to improve poor prognosis of OS due to resistance to chemotherapy remains a challenge. Recently, growing findings show activation of mammalian target of rapamycin (mTOR), is associated with OS cell growth, proliferation, metastasis. Targeting mTOR may be a promising therapeutic approach for treating OS. This review summarizes the roles of mTOR pathway in OS and present research status of mTOR inhibitors in the context of OS. In addition, we have attempted to discuss how to design a better treatment project for OS by combining mTOR inhibitor with other drugs.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Bone Neoplasms; Cell Enlargement; Cell Proliferation; Humans; Neoplasm Metastasis; Osteosarcoma; Prognosis; TOR Serine-Threonine Kinases
PubMed: 27177330
DOI: 10.18632/oncotarget.9305