Exploration of Targeted Anti-tumor Therapy

Table 2. Molecular characteristics and precision oncology implications across major bone sarcoma subtypes.

Subtype	Dominant genomic architecture	Highest-yield profiling targets	Primary precision output	Main limitation
Osteosarcoma	Complex-karyotype; chromosomal instability	Copy-number alterations, structural variants, pathway-state inference	Biological risk stratification; candidate targets often pathway-level	Actionability is diffuse; matched therapy benefit inconsistent
Ewing sarcoma	Fusion-driven (EWSR1–ETS); low mutation burden	Fusion identification/breakpoint assays; recurrent events (e.g., STAG2/CDKN2A)	Diagnostic confirmation/refinement; monitoring-amenable biomarkers	Few recurrent druggable point mutations; biomarker validation variable
Chondrosarcoma	Subtype-dependent; metabolic/epigenetic axis common	IDH1/2 status; genomic instability signatures (e.g., LOH burden); transcriptomic state	Molecular subgrouping beyond grade; trial stratification	Clinical translation of subgrouping still limited

Return to article view

EWSR1–ETS: EWS RNA-binding protein 1–ETS transcription factor fusion family; STAG2: stromal antigen 2; CDKN2A: cyclin dependent kinase inhibitor 2A; IDH1/2: isocitrate dehydrogenase 1 and 2; LOH: loss of heterozygosity.

Declarations

Author contributions

SY: Investigation, Writing—original draft. PT: Conceptualization, Writing—review & editing, Validation, Supervision. Both authors read and approved the submitted version.

Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Palmerini E, Righi A, Staals EL. Rare Primary Malignant Bone Sarcomas. Cancers (Basel). 2020;12:3092. [DOI] [PubMed] [PMC]

Reed DR, Hayashi M, Wagner L, Binitie O, Steppan DA, Brohl AS, et al. Treatment pathway of bone sarcoma in children, adolescents, and young adults. Cancer. 2017;123:2206–18. [DOI] [PubMed] [PMC]

Lupo PJ, Spector LG, O’Brien S, Schiffman JD, Hettmer S. Epidemiology of Bone and Soft Tissue Sarcomas. In: Arndt CAS, editor. Sarcomas of Bone and Soft Tissues in Children and Adolescents. Pediatric Oncology. Cham: Springer; 2021. pp. 1–16. [DOI]

Gounder MM, Agaram NP, Trabucco SE, Robinson V, Ferraro RA, Millis SZ, et al. Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma. Nat Commun. 2022;13:3406. [DOI] [PubMed] [PMC]

Khan AA, Kumar R N, Chakma S, Das S. Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects. Pathol Res Pract. 2024;263:155634. [DOI] [PubMed]

Bădilă AE, Rădulescu DM, Niculescu AG, Grumezescu AM, Rădulescu M, Rădulescu AR. Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review. Cancers (Basel). 2021;13:4229. [DOI] [PubMed] [PMC]

Mulita F, Verras GI, Anagnostopoulos CN, Kotis K. A Smarter Health through the Internet of Surgical Things. Sensors (Basel). 2022;22:4577. [DOI] [PubMed] [PMC]

Gerrand C, Amary F, Anwar HA, Brennan B, Dileo P, Kalkat MS, et al. UK guidelines for the management of bone sarcomas. Br J Cancer. 2025;132:32–48. [DOI] [PubMed] [PMC]

Bläsius F, Delbrück H, Hildebrand F, Hofmann UK. Surgical Treatment of Bone Sarcoma. Cancers (Basel). 2022;14:2694. [DOI] [PubMed] [PMC]

10.

Li X, Moretti VM, Ashana AO, Lackman RD. Impact of close surgical margin on local recurrence and survival in osteosarcoma. Int Orthop. 2012;36:131–7. [DOI] [PubMed] [PMC]

11.

Smolle MA, Kogler A, Andreou D, Scheipl S, Bergovec M, Castellani C, et al. Prognostic Impact of Pulmonary Metastasectomy in Bone Sarcoma Patients: A Retrospective, Single-Centre Study. Cancers (Basel). 2023;15:1733. [DOI] [PubMed] [PMC]

12.

Locquet MA, Brahmi M, Blay JY, Dutour A. Radiotherapy in bone sarcoma: the quest for better treatment option. BMC Cancer. 2023;23:742. [DOI] [PubMed] [PMC]

13.

Wagner MJ, Livingston JA, Patel SR, Benjamin RS. Chemotherapy for Bone Sarcoma in Adults. J Oncol Pract. 2016;12:208–16. [DOI] [PubMed]

14.

Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015;33:3029–35. [DOI] [PubMed] [PMC]

15.

Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016;17:1396–408. [DOI] [PubMed] [PMC]

16.

Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18:609–24. [DOI] [PubMed]

17.

Eaton BR, Claude L, Indelicato DJ, Vatner R, Yeh B, Schwarz R, et al. Ewing sarcoma. Pediatr Blood Cancer. 2021;68 Suppl 2:e28355. [DOI] [PubMed]

18.

MacDonald IJ, Lin CY, Kuo SJ, Su CM, Tang CH. An update on current and future treatment options for chondrosarcoma. Expert Rev Anticancer Ther. 2019;19:773–86. [DOI] [PubMed]

19.

Heymann D, Rédini F. Targeted therapies for bone sarcomas. Bonekey Rep. 2013;2:378. [DOI] [PubMed] [PMC]

20.

Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Tsuchiya H. Therapeutic Targets for Bone and Soft-Tissue Sarcomas. Int J Mol Sci. 2019;20:170. [DOI] [PubMed] [PMC]

21.

Liu Y, Huang N, Liao S, Rothzerg E, Yao F, Li Y, et al. Current research progress in targeted anti-angiogenesis therapy for osteosarcoma. Cell Prolif. 2021;54:e13102. [DOI] [PubMed] [PMC]

22.

Jin H, Huang C, Dong Y, Xiong Q, Wang D, He Z, et al. Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review. Front Oncol. 2026;15:1665299. [DOI] [PubMed] [PMC]

23.

Higuchi T, Igarashi K, Yamamoto N, Hayashi K, Kimura H, Miwa S, et al. Osteosarcoma Patient-derived Orthotopic Xenograft (PDOX) Models Used to Identify Novel and Effective Therapeutics: A Review. Anticancer Res. 2021;41:5865–71. [DOI] [PubMed]

24.

Hu D, Yu X, Xu J, Li B, Ou X, Shi S. Innovative gene targeted treatments for osteosarcoma: a mini review of current clinical evidence and future prospects. Front Med (Lausanne). 2025;12:1699287. [DOI] [PubMed] [PMC]

25.

Pishas KI, Lessnick SL. Recent advances in targeted therapy for Ewing sarcoma. F1000Res. 2016;5:F1000 Faculty Rev–2077. [DOI] [PubMed] [PMC]

26.

Fayzullina D, Tsibulnikov S, Stempen M, Schroeder BA, Kumar N, Kharwar RK, et al. Novel Targeted Therapeutic Strategies for Ewing Sarcoma. Cancers (Basel). 2022;14:1988. [DOI] [PubMed] [PMC]

27.

Loganathan SN, Tang N, Fleming JT, Ma Y, Guo Y, Borinstein SC, et al. BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. Oncotarget. 2016;7:43504–17. [DOI] [PubMed] [PMC]

28.

Welch D, Kahen E, Fridley B, Brohl AS, Cubitt CL, Reed DR. Small molecule inhibition of lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) alone and in combination in Ewing sarcoma cell lines. PLoS One. 2019;14:e0222228. [DOI] [PubMed] [PMC]

29.

Theisen ER, Pishas KI, Saund RS, Lessnick SL. Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. Oncotarget. 2016;7:17616–30. [DOI] [PubMed] [PMC]

30.

Manara MC, Manferdini C, Cristalli C, Carrabotta M, Santi S, De Feo A, et al. Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages. Cancer Immunol Res. 2024;12:247–60. [DOI] [PubMed] [PMC]

31.

Gazendam A, Popovic S, Parasu N, Ghert M. Chondrosarcoma: A Clinical Review. J Clin Med. 2023;12:2506. [DOI] [PubMed] [PMC]

32.

Walter SG, Knöll P, Eysel P, Quaas A, Gaisendrees C, Nißler R, et al. Molecular In-Depth Characterization of Chondrosarcoma for Current and Future Targeted Therapies. Cancers (Basel). 2023;15:2556. [DOI] [PubMed] [PMC]

33.

Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Tsuchiya H. Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma. Int J Mol Sci. 2022;23:1096. [DOI] [PubMed] [PMC]

34.

Polychronidou G, Karavasilis V, Pollack SM, Huang PH, Lee A, Jones RL. Novel therapeutic approaches in chondrosarcoma. Future Oncol. 2017;13:637–48. [DOI] [PubMed]

35.

Fleuren EDG, Vlenterie M, van der Graaf WTA. Recent advances on anti-angiogenic multi-receptor tyrosine kinase inhibitors in osteosarcoma and Ewing sarcoma. Front Oncol. 2023;13:1013359. [DOI] [PubMed] [PMC]

36.

Davis LE, Bolejack V, Ryan CW, Ganjoo KN, Loggers ET, Chawla S, et al. Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. J Clin Oncol. 2019;37:1424–31. [DOI] [PubMed] [PMC]

37.

Duffaud F, Mir O, Boudou-Rouquette P, Piperno-Neumann S, Penel N, Bompas E, et al.; French Sarcoma Group. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2019;20:120–33. [DOI] [PubMed]

38.

Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020;21:446–55. [DOI] [PubMed] [PMC]

39.

Chen C, Shi Q, Xu J, Ren T, Huang Y, Guo W. Current progress and open challenges for applying tyrosine kinase inhibitors in osteosarcoma. Cell Death Discov. 2022;8:488. [DOI] [PubMed] [PMC]

40.

Giacchi L, Pucci E, Rucci N. From Bench to Bedside: Advancements in Precision Oncology and Drug Discovery for Osteosarcoma. Cancers (Basel). 2026;18:561. [DOI] [PubMed] [PMC]

41.

Albarrán V, Villamayor ML, Chamorro J, Rosero DI, Pozas J, San Román M, et al. Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas. Int J Mol Sci. 2022;23:13784. [DOI] [PubMed] [PMC]

42.

Attia S, Bolejack V, Ganjoo KN, George S, Agulnik M, Rushing D, et al. A phase II trial of regorafenib in patients with advanced Ewing sarcoma and related tumors of soft tissue and bone: SARC024 trial results. Cancer Med. 2023;12:1532–9. [DOI] [PubMed] [PMC]

43.

Duffaud F, Blay JY, Mir O, Chevreau CM, Boudou Rouquette P, Kalbacher E, et al. LBA68 Results of the randomized, placebo (PL)-controlled phase II study evaluating the efficacy and safety of regorafenib (REG) in patients (pts) with metastatic relapsed Ewing sarcoma (ES), on behalf of the French Sarcoma Group (FSG) and UNICANCER. Ann Oncol. 2020;31:S1199.

44.

Xu J, Xie L, Sun X, Liu K, Tang X, Yan T, et al. Anlotinib, Vincristine, and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy: A Two-Cohort, Phase Ib/II Trial. Oncologist. 2021;26:e1256–62. [DOI] [PubMed] [PMC]

45.

Wang HY, Chu JF, Zhang P, Wang JQ, Yan Z, Yao SN, et al. Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma. Onco Targets Ther. 2020;13:1561–8. [DOI] [PubMed] [PMC]

46.

Barenboim M, Kovac M, Ameline B, Jones DTW, Witt O, Bielack S, et al. DNA methylation-based classifier and gene expression signatures detect BRCAness in osteosarcoma. PLoS Comput Biol. 2021;17:e1009562. [DOI] [PubMed] [PMC]

47.

Engert F, Kovac M, Baumhoer D, Nathrath M, Fulda S. Osteosarcoma cells with genetic signatures of BRCAness are susceptible to the PARP inhibitor talazoparib alone or in combination with chemotherapeutics. Oncotarget. 2017;8:48794–806. [DOI] [PubMed] [PMC]

48.

Park HJ, Bae JS, Kim KM, Moon YJ, Park SH, Ha SH, et al. The PARP inhibitor olaparib potentiates the effect of the DNA damaging agent doxorubicin in osteosarcoma. J Exp Clin Cancer Res. 2018;37:107. [DOI] [PubMed] [PMC]

49.

Holme H, Gulati A, Brough R, Fleuren EDG, Bajrami I, Campbell J, et al. Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. Sci Rep. 2018;8:10614. [DOI] [PubMed] [PMC]

50.

Brenner JC, Feng FY, Han S, Patel S, Goyal SV, Bou-Maroun LM, et al. PARP-1 inhibition as a targeted strategy to treat Ewing’s sarcoma. Cancer Res. 2012;72:1608–13. [DOI] [PubMed] [PMC]

51.

Ordóñez JL, Amaral AT, Carcaboso AM, Herrero-Martín D, del Carmen García-Macías M, Sevillano V, et al. The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin. Oncotarget. 2015;6:18875–90. [DOI] [PubMed] [PMC]

52.

Xie J, Mellado-Lagarde MM, Blankenship K, Ganguly D, Twarog NR, Bianski B, et al. The Combination of PARP and Topoisomerase 1 Inhibitors Improves Radiation Therapy for Ewing Sarcoma. Cancer Sci. 2025;116:1703–14. [DOI] [PubMed] [PMC]

53.

López-Fuentes E, Clugston AS, Lee AG, Sayles LC, Sorensen N, Pons Ventura MV, et al. Epigenetic and Transcriptional Programs Define Osteosarcoma Subtypes and Establish Targetable Vulnerabilities. Cancer Discov. 2026;16:296–319. [DOI] [PubMed] [PMC]

54.

Yarber JL, Agulnik M. Targeted therapies in bone sarcomas: current approach and future directions. Expert Opin Investig Drugs. 2011;20:973–9. [DOI] [PubMed]

55.

Gaspar N, Di Giannatale A, Geoerger B, Redini F, Corradini N, Enz-Werle N, et al. Bone sarcomas: from biology to targeted therapies. Sarcoma. 2012;2012:301975. [DOI] [PubMed] [PMC]

56.

Brown HK, Schiavone K, Gouin F, Heymann MF, Heymann D. Biology of Bone Sarcomas and New Therapeutic Developments. Calcif Tissue Int. 2018;102:174–95. [DOI] [PubMed] [PMC]

57.

Rickel K, Fang F, Tao J. Molecular genetics of osteosarcoma. Bone. 2017;102:69–79. [DOI] [PubMed] [PMC]

58.

Czarnecka AM, Synoradzki K, Firlej W, Bartnik E, Sobczuk P, Fiedorowicz M, et al. Molecular Biology of Osteosarcoma. Cancers (Basel). 2020;12:2130. [DOI] [PubMed] [PMC]

59.

Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, et al. Ewing sarcoma. Nat Rev Dis Primers. 2018;4:5. [DOI] [PubMed]

60.

Showpnil IA, Selich-Anderson J, Taslim C, Boone MA, Crow JC, Theisen ER, et al. EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma. Nucleic Acids Res. 2022;50:9814–37. [DOI] [PubMed] [PMC]

61.

Cojocaru E, Wilding C, Engelman B, Huang P, Jones RL. Is the IDH Mutation a Good Target for Chondrosarcoma Treatment? Current Molecular Biology Reports. 2020;6:1–9. [DOI]

62.

Gutiérrez-Jimeno M, Alba-Pavón P, Astigarraga I, Imízcoz T, Panizo-Morgado E, García-Obregón S, et al. Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas. Cancers (Basel). 2021;13:5436. [DOI] [PubMed] [PMC]

63.

Norberg SM, Movva S. Role of genetic and molecular profiling in sarcomas. Curr Treat Options Oncol. 2015;16:24. [DOI] [PubMed]

64.

Scotlandi K, Hattinger CM, Pellegrini E, Gambarotti M, Serra M. Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors. Cells. 2020;9:968. [DOI] [PubMed] [PMC]

65.

Xu Y, Bai Y, Yang F, Yang B, Huang Z, Su L, et al. Decoding osteosarcoma from heterogeneity to precision therapy. Discov Oncol. 2025;17:192. [DOI] [PubMed] [PMC]

66.

Southekal S, Shakyawar SK, Bajpai P, Elkholy A, Manne U, Mishra NK, et al. Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways. Cancers (Basel). 2023;15:2134. [DOI] [PubMed] [PMC]

67.

Subbiah V, Wagner MJ, McGuire MF, Sarwari NM, Devarajan E, Lewis VO, et al. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine. Oncotarget. 2015;6:40642–54. [DOI] [PubMed] [PMC]

68.

Chen X, Tian B, Wang Y, Zheng J, Kang X. Harnessing multiomics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review). Int J Mol Med. 2025;55:92. [DOI] [PubMed] [PMC]

69.

Tang S, Roberts RD, Cheng L, Li L. Osteosarcoma Multi-Omics Landscape and Subtypes. Cancers (Basel). 2023;15:4970. [DOI] [PubMed] [PMC]

70.

Hurkmans EGE, Brand ACAM, Verdonschot JAJ, Te Loo DMWM, Coenen MJH. Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review. BMC Cancer. 2022;22:1326. [DOI] [PubMed] [PMC]

71.

Fuloria S, Yadav G, Menon SV, Ali H, Pant K, Kaur M, et al. Targeting the Wnt/β-catenin cascade in osteosarcoma: The potential of ncRNAs as biomarkers and therapeutics. Pathol Res Pract. 2024;259:155346. [DOI] [PubMed]

72.

Anderson N. Mutation Evolution and Genomic Patterns of Recurrence in Ewing Sarcoma and Leiomyosarcoma [dissertation]. Canada: University of Toronto; 2020.

73.

Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 2014;4:1326–41. [DOI] [PubMed]

74.

Salguero-Aranda C, Amaral AT, Olmedo-Pelayo J, Diaz-Martin J, Álava E. Breakthrough Technologies Reshape the Ewing Sarcoma Molecular Landscape. Cells. 2020;9:804. [DOI] [PubMed] [PMC]

75.

Jo VY. EWSR1 fusions: Ewing sarcoma and beyond. Cancer Cytopathol. 2020;128:229–31. [DOI] [PubMed]

76.

AlDoughaim M, AlSuhebany N, AlZahrani M, AlQahtani T, AlGhamdi S, Badreldin H, et al. Cancer Biomarkers and Precision Oncology: A Review of Recent Trends and Innovations. Clin Med Insights Oncol. 2024;18:11795549241298541. [DOI] [PubMed] [PMC]

77.

Goodspeed A, Bodlak A, Duffy AB, Nelson-Taylor S, Oike N, Porfilio T, et al. Single-Cell RNA Sequencing of Ewing Sarcoma Tumors Demonstrates Transcriptional Heterogeneity and Clonal Evolution. Clin Cancer Res. 2025;31:2010–23. [DOI] [PubMed] [PMC]

78.

Ou X, Gao G, Ma Q, Qin D, Li K, Feng M, et al. KC1036, a multi-kinase inhibitor with anti-angiogenic activity, can effectively suppress the tumor growth of Ewing sarcoma. Angiogenesis. 2025;28:50. [DOI] [PubMed]

79.

Knott MML, Hölting TLB, Ohmura S, Kirchner T, Cidre-Aranaz F, Grünewald TGP. Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies. Cancer Metastasis Rev. 2019;38:625–42. [DOI] [PubMed] [PMC]

80.

Landuzzi L, Ruzzi F, Lollini PL, Scotlandi K. Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches. Int J Mol Sci. 2025;26:1542. [DOI] [PubMed] [PMC]

81.

Setola E. Microenvironment and prognostic factors in bone tumors: IDH mutations in chondrosarcoma [dissertation]. Università di Bologna; 2022.

82.

Deshmukh S, Kelly C, Tinoco G. IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma. Target Oncol. 2025;20:13–25. [DOI] [PubMed] [PMC]

83.

Iacobescu GL, Corlatescu AD, Serban B, Spiridonica R, Costin HP, Cirstoiu C. Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature. Curr Issues Mol Biol. 2024;46:12658–71. [DOI] [PubMed] [PMC]

84.

Oliva-Ramirez J, Milewski D, Banks L, Bailey KM, Moding EJ, Lake J, et al. Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout. Cancers (Basel). 2025;17:3068. [DOI] [PubMed] [PMC]

85.

Li S, Zhang H, Shang G. Current status and future challenges of CAR-T cell therapy for osteosarcoma. Front Immunol. 2023;14:1290762. [DOI] [PubMed] [PMC]

86.

Phase I Study of B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults [Internet]. [cited 2026 Aug 6]. Available from: https://www.medifind.com/articles/clinical-trial/227351331

87.

Fradin JJ, Charlson JA. Review of Adoptive Cellular Therapies for the Treatment of Sarcoma. Cancers (Basel). 2025;17:1302. [DOI] [PubMed] [PMC]

88.

O’Reilly C, Tuladhar S, Nguyen P, Sheppard H, Koo SC, Chockley P, et al. LRRC15-CAR T Cells for the Treatment of Osteosarcoma. Clin Cancer Res. 2026;32:1557–73. [DOI] [PubMed] [PMC]

89.

Heymann MF, Schiavone K, Heymann D. Bone sarcomas in the immunotherapy era. Br J Pharmacol. 2021;178:1955–72. [DOI] [PubMed]

90.

Englisch A, Altvater B, Kailayangiri S, Hartmann W, Rossig C. VEGFR2 as a target for CAR T cell therapy of Ewing sarcoma. Pediatr Blood Cancer. 2020;67:e28313. [DOI] [PubMed]

91.

Dong C, Beglinger I, Krieg AH. Personalized 3D-printed guide in malignant bone tumor resection and following reconstruction - 17 cases in pelvic and extremities. Surg Oncol. 2022;42:101733. [DOI] [PubMed]

92.

Osei-Hwedieh DO, He L, Wang K, Fan S, Ferrone S, Wang X, et al. HDAC inhibitor (SAHA) enhances B7-H3-specific CAR T cell cytotoxic efficacy against chondrosarcoma cells and prolongs survival in an orthotopic mouse model. Transl Oncol. 2025;62:102538. [DOI] [PubMed] [PMC]

93.

Xie L, Chen C, Liang X, Xu J, Sun X, Sun K, et al. Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy. Orthop Surg. 2023;15:829–38. [DOI] [PubMed] [PMC]

94.

Nathenson MJ, Conley AP, Sausville E. Immunotherapy: A New (and Old) Approach to Treatment of Soft Tissue and Bone Sarcomas. Oncologist. 2018;23:71–83. [DOI] [PubMed] [PMC]

95.

Panagi M, Pilavaki P, Constantinidou A, Stylianopoulos T. Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness. Theranostics. 2022;12:6106–29. [DOI] [PubMed] [PMC]

96.

Birdi HK, Jirovec A, Cortés-Kaplan S, Werier J, Nessim C, Diallo JS, et al. Immunotherapy for sarcomas: new frontiers and unveiled opportunities. J Immunother Cancer. 2021;9:e001580. [DOI] [PubMed] [PMC]

97.

Nakano K. Challenges of Systemic Therapy Investigations for Bone Sarcomas. Int J Mol Sci. 2022;23:3540. [DOI] [PubMed] [PMC]

98.

Tlemsani C, Larousserie F, De Percin S, Audard V, Hadjadj D, Chen J, et al. Biology and Management of High-Grade Chondrosarcoma: An Update on Targets and Treatment Options. Int J Mol Sci. 2023;24:1361. [DOI] [PubMed] [PMC]

99.

Zhu GG, Nafa K, Agaram N, Zehir A, Benayed R, Sadowska J, et al. Genomic Profiling Identifies Association of IDH1/IDH2 Mutation with Longer Relapse-Free and Metastasis-Free Survival in High-Grade Chondrosarcoma. Clin Cancer Res. 2020;26:419–27. [DOI] [PubMed] [PMC]

100.

Hirata M, Sasaki M, Cairns RA, Inoue S, Puviindran V, Li WY, et al. Mutant IDH is sufficient to initiate enchondromatosis in mice. Proc Natl Acad Sci U S A. 2015;112:2829–34. [DOI] [PubMed] [PMC]

101.

Tap WD, Villalobos VM, Cote GM, Burris H, Janku F, Mir O, et al. Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. J Clin Oncol. 2020;38:1693–701. [DOI] [PubMed] [PMC]

102.

Micaily I, Roche M, Ibrahim MY, Martinez-Outschoorn U, Mallick AB. Metabolic Pathways and Targets in Chondrosarcoma. Front Oncol. 2021;11:772263. [DOI] [PubMed] [PMC]

103.

Addie RD, de Jong Y, Alberti G, Kruisselbrink AB, Que I, Baelde H, et al. Exploration of the chondrosarcoma metabolome; the mTOR pathway as an important pro-survival pathway. J Bone Oncol. 2019;15:100222. [DOI] [PubMed] [PMC]

104.

Molina ER, Chim LK, Barrios S, Ludwig JA, Mikos AG. Modeling the Tumor Microenvironment and Pathogenic Signaling in Bone Sarcoma. Tissue Eng Part B Rev. 2020;26:249–71. [DOI] [PubMed] [PMC]

105.

Gao S, Shen J, Hornicek F, Duan Z. Three-dimensional (3D) culture in sarcoma research and the clinical significance. Biofabrication. 2017;9:032003. [DOI] [PubMed]

106.

Chaddad H. Development of vascularized tumor spheroids mimicking the tumor environment: angiogenesis and hypoxia [dissertation]. Université de Strasbourg; 2019.

107.

Colella G, Fazioli F, Gallo M, De Chiara A, Apice G, Ruosi C, et al. Sarcoma Spheroids and Organoids-Promising Tools in the Era of Personalized Medicine. Int J Mol Sci. 2018;19:615. [DOI] [PubMed] [PMC]

108.

Shah S, D’Souza GGM. Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis. Cells. 2025;14:732. [DOI] [PubMed] [PMC]

109.

Koushik TM, Miller CM, Antunes E. Bone Tissue Engineering Scaffolds: Function of Multi-Material Hierarchically Structured Scaffolds. Adv Healthc Mater. 2023;12:e2202766. [DOI] [PubMed] [PMC]

110.

Huang D, Li Z, Li G, Zhou F, Wang G, Ren X, et al. Biomimetic structural design in 3D-printed scaffolds for bone tissue engineering. Mater Today Bio. 2025;32:101664. [DOI] [PubMed] [PMC]

111.

Jing Z, Yuan W, Wang J, Ni R, Qin Y, Mao Z, et al. Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects. Bioact Mater. 2023;33:223–41. [DOI] [PubMed] [PMC]

112.

Rong X, Xiao S, Geng W, Zhu B, Mou P, Ding Z, et al. Sono-activable and biocatalytic 3D-printed scaffolds for intelligently sequential therapies in osteosarcoma eradication and defect regeneration. Nat Commun. 2025;16:6150. [DOI] [PubMed] [PMC]

113.

Alaribe FN, Manoto SL, Motaung SC. Scaffolds from biomaterials: advantages and limitations in bone and tissue engineering. Biologia. 2016;71:353–66. [DOI]

114.

Xu S, Tan S, Guo L. Patient-Derived Organoids as a Promising Tool for Multimodal Management of Sarcomas. Cancers (Basel). 2023;15:4339. [DOI] [PubMed] [PMC]

115.

Nie JH, Wan CY, Li H, Zhou JL, Zhong GQ, Yang T, et al. Personalized prediction of chemotherapy efficacy in osteosarcoma through patient-derived organoids: correlation with survival and tumor proliferation potential. J Exp Clin Cancer Res. 2025;45:16. [DOI] [PubMed] [PMC]

116.

Taurin S, Alzahrani R, Aloraibi S, Ashi L, Alharmi R, Hassani N. Patient-derived tumor organoids: A preclinical platform for personalized cancer therapy. Transl Oncol. 2025;51:102226. [DOI] [PubMed] [PMC]

117.

Liu Y, Wu W, Cai C, Zhang H, Shen H, Han Y. Patient-derived xenograft models in cancer therapy: technologies and applications. Signal Transduct Target Ther. 2023;8:160. [DOI] [PubMed] [PMC]

118.

Higuchi T, Hoffman RM, Tsuchiya H, Yamamoto N, Hayashi K, Miwa S, et al. Osteosarcoma patient-derived orthotopic xenograft (PDOX) models for identification of novel and effective therapeutics. J Clin Oncol. 2024;42:228. [DOI]

119.

Liu M, Yang X. Patient-derived xenograft models: Current status, challenges, and innovations in cancer research. Genes Dis. 2025;12:101520. [DOI] [PubMed] [PMC]

120.

Liu J, Ren B, He T, Li D, Ding T, Wang Q, et al. Engineering Osteosarcoma In Vitro: From Traditional Models to Biofabricated Platforms for Precision Medicine. ACS Omega. 2025;10:55219–33. [DOI] [PubMed] [PMC]

121.

Chow T, Wutami I, Lucarelli E, Choong PF, Duchi S, Di Bella C. Creating In Vitro Three-Dimensional Tumor Models: A Guide for the Biofabrication of a Primary Osteosarcoma Model. Tissue Eng Part B Rev. 2021;27:514–29. [DOI] [PubMed]

122.

Domingues MF, Silva JC, Sanjuan‐Alberte P. From spheroids to bioprinting: a literature review on biomanufacturing strategies of 3D in vitro osteosarcoma models. Adv Ther. 2024;7:2400047. [DOI]

123.

Smolle MA, Seidel MG, Kashofer K, Liegl-Atzwanger B, Sadoghi P, Müller DA, et al. Precision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review. Arch Orthop Trauma Surg. 2025;145:121. [DOI] [PubMed] [PMC]

124.

Ucci A, Rucci N, Ponzetti M. Liquid biopsies in primary and secondary bone cancers. Cancer Drug Resist. 2022;5:541–59. [DOI] [PubMed] [PMC]

125.

Li X, Seebacher NA, Hornicek FJ, Xiao T, Duan Z. Application of liquid biopsy in bone and soft tissue sarcomas: Present and future. Cancer Lett. 2018;439:66–77. [DOI] [PubMed]

126.

Allegretti M, Casini B, Mandoj C, Benini S, Alberti L, Novello M, et al. Precision diagnostics of Ewing's sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts. Ther Adv Med Oncol. 2018;10:1758835918774337. [DOI] [PubMed] [PMC]

127.

Seidel MG, Kashofer K, Moser T, Thueringer A, Liegl-Atzwanger B, Leithner A, et al. Clinical implementation of plasma cell-free circulating tumor DNA quantification by digital droplet PCR for the monitoring of Ewing sarcoma in children and adolescents. Front Pediatr. 2022;10:926405. [DOI] [PubMed] [PMC]

128.

Fu Y, Xu Y, Liu W, Zhang J, Wang F, Jian Q, et al. Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcoma. EClinicalMedicine. 2024;73:102697. [DOI] [PubMed] [PMC]

129.

Shulman DS, Crompton BD. Using Liquid Biopsy in the Treatment of Patient with OS. Adv Exp Med Biol. 2020;1257:95–105. [DOI] [PubMed]

130.

van der Laan P, van Houdt WJ, van den Broek D, Steeghs N, van der Graaf WTA. Liquid Biopsies in Sarcoma Clinical Practice: Where Do We Stand? Biomedicines. 2021;9:1315. [DOI] [PubMed] [PMC]

131.

Aran V, Devalle S, Meohas W, Heringer M, Cunha Caruso A, Pinheiro Aguiar D, et al. Osteosarcoma, chondrosarcoma and Ewing sarcoma: Clinical aspects, biomarker discovery and liquid biopsy. Crit Rev Oncol Hematol. 2021;162:103340. [DOI] [PubMed]

132.

Aiyer S, Kim TH, Collier K, Pollock R, Verschraegen C, Stover DG, et al. Unlocking the Potential of ctDNA in Sarcomas: A Review of Recent Advances. Cancers (Basel). 2025;17:1040. [DOI] [PubMed] [PMC]

133.

Agnoletto C, Caruso C, Garofalo C. Heterogeneous Circulating Tumor Cells in Sarcoma: Implication for Clinical Practice. Cancers (Basel). 2021;13:2189. [DOI] [PubMed] [PMC]

134.

Tan L, Wang Y, Hu X, Min L. The Roles of Exosomes in Metastasis of Sarcoma: From Biomarkers to Therapeutic Targets. Biomolecules. 2023;13:456. [DOI] [PubMed] [PMC]

135.

Tamura T, Yoshioka Y, Sakamoto S, Ichikawa T, Ochiya T. Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets. Int J Mol Sci. 2020;21:6680. [DOI] [PubMed] [PMC]

136.

Jamil NY, Nawrooz MS, Bishoyi AK, Ballal S, Singh A, Krithiga T, et al. The therapeutic potential of exosomes in bone cancers: osteosarcoma, chondrosarcoma, and Ewing sarcoma. Invest New Drugs. 2025;43:991–1012. [DOI] [PubMed]

137.

Liao Y, Yi Q, He J, Huang D, Xiong J, Sun W, et al. Extracellular vesicles in tumorigenesis, metastasis, chemotherapy resistance and intercellular communication in osteosarcoma. Bioengineered. 2023;14:113–28. [DOI] [PubMed] [PMC]

138.

Li S. The basic characteristics of extracellular vesicles and their potential application in bone sarcomas. J Nanobiotechnology. 2021;19:277. [DOI] [PubMed] [PMC]

139.

Wang Y, Fujiwara T, Kurozumi T, Ando T, Ishimaru T, Kondo H, et al. Advances in liquid biopsy for bone and soft-tissue sarcomas. Int J Clin Oncol. 2025;30:1722–33. [DOI] [PubMed] [PMC]

140.

Wallander K, Öfverholm I, Boye K, Tsagkozis P, Papakonstantinou A, Lin Y, et al. Sarcoma care in the era of precision medicine. J Intern Med. 2023;294:690–707. [DOI] [PubMed]

141.

Czarnecka AM, Błoński P, Chmiel P, Rutkowski P. Novel biomarkers in bone sarcomas—diagnosis, treatment selection, and clinical trials. Oncol Clin Pract. 2025;21:154–65. [DOI]

142.

Elshimy Y, Alkhatib AR, Atassi B, Mohammad KS. Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications. Biomedicines. 2025;13:1160. [DOI] [PubMed] [PMC]

143.

Rajan S, Zaccaria S, Cannon MV, Cam M, Gross AC, Raphael BJ, et al. Structurally Complex Osteosarcoma Genomes Exhibit Limited Heterogeneity within Individual Tumors and across Evolutionary Time. Cancer Res Commun. 2023;3:564–75. [DOI] [PubMed] [PMC]