[1] [1] TLEMSANI C, LAROUSSERIE F, DE PERCIN S,et al. Biology and management of high-grade chondrosarcoma: an update on targets and treatment options[J/OL]. Int J Mol Sci, 2023, 24(2): 1361[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/36674874/. DOI:10.3390/ijms24021361.

[2] [2] GAZENDAM A, POPOVIC S, PARASU N,et al. Chondrosarcoma: a clinical review[J/OL]. J Clin Med, 2023, 12(7): 2506[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37048590/. DOI:10.3390/jcm12072506.

[3] [3] MIWA S, YAMAMOTO N, HAYASHI K,et al. Therapeutic targets and emerging treatments in advanced chondrosarcoma[J/OL]. Int J Mol Sci, 2022, 23(3): 1096[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/35163019/. DOI:10.3390/ijms23031096.

[4] [4] TANG Q, CHEN Y, LI X J,et al. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers[J/OL]. Front Immunol, 2022, 13: 964442[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/36177034/. DOI:10.3389/fimmu.2022.964442.

[5] [5] COHEN-NOWAK A J, DRESSLER D B, ROCK A,et al. Role of immunotherapy in chondrosarcoma: a case report and review of the literature[J/OL]. Ther Adv Med Oncol, 2023, 15: 17588359231199877[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37745839/. DOI:10.1177/17588359231199877.

[6] [6] AGARWAL S, RATHI A K, SINGH K,et al. Extracorporeal irradiation in malignant bone tumors: Single institution experience and review of literature[J]. J Cancer Res Ther, 2023, 19(Supplement): S1-S5. DOI:10.4103/jcrt.jcrt_1316_21.

[7] [7] VAN DER GEEST I M, DE VALK M H, DE ROOY J J,et al. Oncological and functional results of cryosurgical therapy of enchondromas and chondrosarcomas grade 1[J]. J Surg Oncol,2008, 98(6): 421-426. DOI:10.1002/jso.21122.

[8] [8] SHARMA V, VERMA L, CHANDER B,et al. Chondrosarcoma third metacarpal: Diagnosis and management options[J]. J Cancer Res Ther, 2018, 14(3): 719-721. DOI:10.4103/0973-1482.175429.

[9] [9] GILBERT A, TUDOR M, MONTANARI J,et al. Chondrosarcoma resistance to radiation therapy: origins and potential therapeutic solutions[J/OL]. Cancers, 2023, 15(7): 1962[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37046623/. DOI:10.3390/cancers15071962.

[10] [10] MACDONALD I J, LIN C Y, KUO S J,et al. An update on current and future treatment options for chondrosarcoma[J]. Expert Rev Anticancer Ther, 2019, 19(9): 773-786. DOI:10.1080/14737140.2019.1659731.

[11] [11] POTTER G M, SIRIPURAPU R, HERWADKAR A,et al. Skull base chordoma and chondrosarcoma: neuroradiologist's guide to diagnosis, surgical management, and proton beam therapy[J/OL]. Radiographics, 2024, 44(10): e240036[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/39298353/. DOI:10.1148/rg.240036.

[12] [12] SHERRY A D, MAROONGROGE S, DE B,et al. Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery[J]. J Neurooncol,2023, 164(2): 377-386. DOI:10.1007/s11060-023-04432-1.

[13] [13] LEMAEVA A A, GULIDOV I A. Radiation therapy for chordomas and chondrosarcomas of the skull base: evaluation of the effectiveness of treatment methods (review)[J]. Sovrem Tekhnologii Med, 2023, 15(5): 44-52. DOI:10.17691/stm2023.15.5.05.

[14] [14] JEYS L M, THORKILDSEN J, KURISUNKAL V,et al. Controversies in orthopaedic oncology[J]. Bone Joint J, 2024, 106-B(5): 425-429. DOI:10.1302/0301-620X.106B5.BJJ-2023-1381.

[15] [15] DANTONELLO T M, INT-VEEN C, LEUSCHNER I,et al. Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups[J]. Cancer, 2008, 112(11): 2424-2431. DOI:10.1002/cncr.23457.

[16] [16] MITCHELL A D, AYOUB K, MANGHAM D C,et al. Experience in the treatment of dedifferentiated chondrosarcoma[J]. J Bone Joint Surg Br, 2000, 82(1): 55-61. DOI:10.1302/0301-620x.82b1.9020.

[17] [17] JEYS L M, MORRIS G V, KURISUNKAL V J,et al. Identifying consensus and areas for future research in chondrosarcoma: a report from the Birmingham Orthopaedic Oncology Meeting[J]. Bone Joint J, 2025, 107-B(2): 246-252. DOI:10.1302/0301-620X.107B2. BJJ-2024-0643.R1.

[18] [18] FREZZA A M, CESARI M, BAUMHOER D,et al. Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study[J]. Eur J Cancer, 2015, 51(3): 374-381. DOI:10.1016/j.ejca.2014.11.007.

[19] [19] MOVVA S, SEIER K, AVUTU V,et al. Histology-specific clinical trial of lenvatinib and pembrolizumab in patients with sarcoma[J]. Clin Cancer Res, 2024, 30(24): 5612-5619. DOI:10.1158/1078-0432.CCR-24-2519.

[20] [20] OUYANG Z X, WANG S S, ZENG M,et al. Therapeutic effect of palbociclib in chondrosarcoma: implication of cyclin-dependent kinase 4 as a potential target[J/OL]. Cell Commun Signal, 2019, 17(1): 17[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/30808351/. DOI:10.1186/s12964-019-0327-5.

[21] [21] JONES R L, KATZ D, LOGGERS E T,et al. Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma[J/OL]. Med Oncol, 2017, 34(10): 167[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/28852958/. DOI:10.1007/s12032-017-1030-2.

[22] [22] HANNA A, SHEVDE L A. Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment[J]. Mol Cancer,2016, 15: 24. DOI:10.1186/s12943-016-0509-3.

[23] [23] WU M H, HUANG P H, HSIEH M,et al. Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300[J]. Oncotarget, 2016, 7(43): 70232-70246. DOI:10.18632/oncotarget.11835.

[24] [24] TSAI C H, YANG D Y, LIN C Y,et al. Sphingosine-1-phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR-101 expression[J]. Mol Oncol, 2017, 11(10): 1380-1398. DOI:10.1002/1878-0261.12106.

[25] [25] LIN C Y, WANG S W, CHEN Y L,et al. Brain-derived neurotrophic factor promotes VEGF-C-dependent lymphangiogenesis by suppressing miR-624-3p in human chondrosarcoma cells[J/OL]. Cell Death Dis, 2017, 8(8): e2964[2025-03-22]. https://pmc.ncbi.nih.gov/articles/PMC5596545/. DOI:10.1038/cddis.2017.354.

[26] [26] YANG X, ZHU G X, YANG Z J,et al. Expression of PD-L1/PD-L2 is associated with high proliferation index of Ki-67 but not with TP53 overexpression in chondrosarcoma[J]. Int J Biol Markers,2018, 33(4): 507-513. DOI:10.1177/1724600818774464.

[27] [27] BORUAH M, GADDAM P, AGARWAL S,et al. PD-L1 expression in rare and aggressive thyroid cancers: a preliminary investigation for a role of immunotherapy[J]. J Cancer Res Ther, 2023, 19(2):312-320. DOI:10.4103/jcrt.jcrt_1471_22.

[28] [28] KOSTINE M, CLEVEN A H, DE MIRANDA N F C C,et al. Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype[J]. Mod Pathol, 2016, 29(9): 1028-1037. DOI:10.1038/modpathol.2016.108.

[29] [29] CHEN Y H, GUO Y J, LIU Z G,et al. An overview of current advances of PD-L1 targeting immuno-imaging in cancers[J]. J Cancer Res Ther,2023, 19(4): 866-875. DOI:10.4103/jcrt.jcrt_88_23.

[30] [30] POLYCHRONIDOU G, KARAVASILIS V, POLLACK S M,et al. Novel therapeutic approaches in chondrosarcoma[J]. Future Oncol,2017, 13(7): 637-648. DOI:10.2217/fon-2016-0226.

[31] [31] CARBONE D P, RECK M, PAZ-ARES L,et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer[J]. N Engl J Med,2017, 376(25): 2415-2426. DOI:10.1056/NEJMoa1613493.

[32] [32] TAWBI H A, BURGESS M, BOLEJACK V,et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial[J]. Lancet Oncol, 2017, 18(11): 1493-1501. DOI:10.1016/S1470-2045(17)30624-1.

[33] [33] WU Q, JIANG L, LI S C,et al. Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway[J]. Acta Pharmacol Sin, 2021,42(1): 1-9. DOI:10.1038/s41401-020-0366-x.

[34] [34] SHEPPARD K A, FITZ L J, LEE J M,et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta[J]. FEBS Lett,2004, 574(1/2/3): 37-41. DOI:10.1016/j.febslet.2004.07.083.

[35] [35] PATSOUKIS N, BROWN J, PETKOVA V,et al. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation[J/OL]. Sci Signal,2012, 5(230): ra46[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/22740686/. DOI:10.1126/scisignal.2002796.

[36] [36] LEI Q Y, WANG D, SUN K,et al. Resistance mechanisms of anti-PD1/PDL1 therapy in solid tumors[J/OL]. Front Cell Dev Biol, 2020, 8: 672[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/32793604/. DOI:10.3389/fcell.2020.00672.

[37] [37] ZHANG S L, BAI X L, SHAN F P. The progress and confusion of anti-PD1/PD-L1 immunotherapy for patients with advanced non-small cell lung cancer[J/OL]. Int Immunopharmacol, 2020, 80:106247[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/32007710/. DOI:10.1016/j.intimp.2020.106247.

[38] [38] PAOLUZZI L, CACAVIO A, GHESANI M,et al. Response to anti-PD1 therapy with nivolumab in metastatic sarcomas[J/OL]. Clin Sarcoma Res, 2016, 6: 24[2025-03-22]. https://pmc.ncbi.nlm.nih.gov/articles/PMC5200964/. DOI:10.1186/s13569-016-0064-0.

[39] [39] TRAYLOR J I, PERNIK M N, PLITT A R,et al. Immunotherapy for chordoma and chondrosarcoma: current evidence[J/OL]. Cancers, 2021, 13(10): 2408[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/34067530/. DOI:10.3390/cancers13102408.

[40] [40] KEEFE A D, PAI S, ELLINGTON A. Aptamers as therapeutics[J]. Nat Rev Drug Discov, 2010, 9(7): 537-550. DOI:10.1038/nrd3141.

[41] [41] SASIKUMAR P G, RAMACHANDRA R K, ADURTHI S,et al. A rationally designed peptide antagonist of the PD-1 signaling pathway as an immunomodulatory agent for cancer therapy[J]. Mol Cancer Ther, 2019, 18(6): 1081-1091. DOI:10.1158/1535-7163.MCT-18-0737.

[42] [42] LIU J H, CHEN Z C, LI Y Q,et al. PD-1/PD-L1 checkpoint inhibitors in tumor immunotherapy[J/OL]. Front Pharmacol, 2021, 12: 731798 [2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/34539412/. DOI:10.3389/fphar.2021.731798.

[43] [43] KOTRAIAH V, PHARES T W, BROWNE C D,et al. Novel peptide-based PD1 immunomodulators demonstrate efficacy in infectious disease vaccines and therapeutics[J/OL]. Front Immunol,2020, 11: 264[2025-03-22]. https://pmc.nibi.nlm.nih.gov/articles/PMC7068811/. DOI:10.3389/fimmu.2020.00264.

[44] [44] LJUNGGREN H G, JONSSON R, HGLUND P. Seminal immunologic discoveries with direct clinical implications: The 2018 Nobel Prize in Physiology or Medicine honours discoveries in cancer immunotherapy[J/OL]. Scand J Immunol, 2018, 88(6):e12731[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/30485497/. DOI:10.1111/sji.12731.

[45] [45] HAN Y Y, LIU D D, LI L H. PD-1/PD-L1 pathway: current researches in cancer[J]. Am J Cancer Res, 2020, 10(3): 727-742.

[46] [46] GHOSH C, LUONG G, SUN Y. A snapshot of the PD-1/PD-L1 pathway[J]. J Cancer, 2021, 12(9): 2735-2746. DOI:10.7150/jca.57334.

[47] [47] POLLACK S M, REDMAN M W, BAKER K K,et al. Assessment of doxorubicin and pembrolizumab in patients with advanced anthracycline-naive sarcoma: a phase 1/2 nonrandomized clinical trial[J]. JAMA Oncol, 2020, 6(11): 1778-1782. DOI:10.1001/jamaoncol.2020.3689.

[48] [48] LI K H C, GULIA A, DUFFAUD F,et al. Advancing systemic therapy in chondrosarcoma: new horizons[J]. Oncol Ther, 2025, 13(1): 1-9. DOI:10.1007/s40487-024-00317-z.

[49] [49] EL BEAINO M, HODA S T, ELDEIB A J,et al. Dedifferentiated chondrosarcoma: diagnostic controversies and emerging therapeutic targets[J]. Curr Oncol Rep, 2023, 25(10): 1117-1126. DOI:10.1007/s11912-023-01441-1.

[50] [50] YI M, ZHENG X L, NIU M K,et al. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions[J/OL]. Mol Cancer, 2022, 21(1): 28[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/35062949/. DOI:10.1186/s12943-021-01489-2.

[51] [51] KUMAR S, CHATTERJEE M, GHOSH P,et al. Targeting PD-1/PD-L1 in cancer immunotherapy: an effective strategy for treatment of triple-negative breast cancer (TNBC) patients[J]. Genes Dis,2022, 10(4): 1318-1350. DOI:10.1016/j.gendis.2022.07.024.

[52] [52] LI Z T, SUN G Q, SUN G S,et al. Various uses of PD1/PD-L1 inhibitor in oncology: opportunities and challenges[J/OL]. Front Oncol, 2021, 11: 771335[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/34869005/. DOI:10.3389/fonc.2021.771335.

[53] [53] MEFTAHPOUR V, AGHEBATI-MALEKI A, FOTOUHI A,et al. Prognostic significance and therapeutic potentials of immune checkpoints in osteosarcoma[J]. EXCLI J, 2022, 21: 250-268. DOI:10.17179/excli2021-4094.

[54] [54] D'ANGELO S P, MAHONEY M R, VAN TINE B A,et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials[J]. Lancet Oncol, 2018, 19(3): 416-426. DOI:10.1016/S1470-2045(18)30006-8.

[55] [55] WOJTUKIEWICZ M Z, REK M M, KARPOWICZ K,et al. Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners[J]. Cancer Metastasis Rev, 2021, 40(3):949-982. DOI:10.1007/s10555-021-09976-0.

[56] [56] GOEL S, DECRISTO M J, WATT A C,et al. CDK4/6 inhibition triggers anti-tumour immunity[J]. Nature, 2017, 548(7668): 471-475. DOI:10.1038/nature23465.

[57] [57] LI Y, LIU Y H, QU Y C,et al. Case report: two cases of soft-tissue sarcomas: high TMB as a potential predictive biomarker for anlotinib combined with toripalimab therapy[J/OL]. Front Immunol, 2022, 13: 832593[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/35603147/. DOI:10.3389/fimmu.2022.832593.

[58] [58] TANG L N, NIU X H, WANG Z,et al. Anlotinib for recurrent or metastatic primary malignant bone tumor: a multicenter, single-arm trial[J/OL]. Front Oncol, 2022, 12: 811687[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/35692789/. DOI:10.3389/fonc.2022.811687.

[59] [59] BUI N, DIETZ H, FARAG S,et al. A retrospective multi-institutional cohort analysis of clinical characteristics and outcomes in dedifferentiated chondrosarcoma[J/OL]. Cancers, 2023, 15(9):2617[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37174084/. DOI:10.3390/cancers15092617.

[60] [60] TURCAN S, ROHLE D, GOENKA A,et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype[J]. Nature, 2012, 483(7390): 479-483. DOI:10.1038/nature10866.

[61] [61] IVANOV S, NANO O, HANA C,et al. Molecular targeting of the isocitrate dehydrogenase pathway and the implications for cancer therapy[J/OL]. Int J Mol Sci, 2024, 25(13): 7337[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/39000443/. DOI:10.3390/ijms25137337.

[62] [62] WEBER V, ARNAUD L, DUKIC-STEFANOVIC S,et al. Novel radioiodinated and radiofluorinated analogues of FT-2102 for SPECT or PET imaging of mIDH1 mutant tumours[J/OL]. Molecules, 2022, 27(12): 3766[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/35744895/. DOI:10.3390/molecules27123766.

[63] [63] TAP W D, COTE G M, BURRIS H,et al. Phase Ⅰ study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma[J]. Clin Cancer Res, 2025, 31(11): 2108-2114. DOI:10.1158/1078-0432.ccr-24-4128.

[64] [64] VICTOR C T, RECH A J, MAITY A,et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J]. Nature, 2015, 520(7547): 373-377. DOI:10.1038/nature14292.

[65] [65] KORPICS M C, POLLEY M Y, BHAVE S R,et al. A validated T cell radiomics score is associated with clinical outcomes following multisite SBRT and pembrolizumab[J]. Int J Radiat Oncol Biol Phys, 2020, 108(1): 189-195. DOI:10.1016/j.ijrobp.2020.06.026.

[66] [66] NGUYEN B T, LIN C Y, CHANG T K,et al. Melatonin inhibits chondrosarcoma cell proliferation and metastasis by enhancing miR-520f-3p production and suppressing MMP7 expression[J/OL]. J Pineal Res, 2023, 75(1): e12872[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37057370/. DOI:10.1111/jpi.12872.

[67] [67] XU B S, PAN Q Z, PAN H,et al. Anlotinib as a maintenance treatment for advanced soft tissue sarcoma after first-line chemotherapy (ALTER-S006): a multicentre, open-label, singlearm, phase 2 trial[J/OL]. EClinicalMedicine, 2023, 64: 102240[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/37767191/. DOI:10.1016/j.eclinm.2023.102240.

[68] [68] YIN J W, REN P. New advances in the treatment of chondrosarcoma under the PD-1/PD-L1 pathway[J]. J Cancer Res Ther, 2024, 20(2):522-530. DOI:10.4103/jcrt.jcrt_2269_23.

[69] [69] HICKS K C, FANTINI M, DONAHUE R N,et al. Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types[J/OL]. Oncoimmunology,2018, 7(11): e1466018[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/30377559/. DOI:10.1080/2162402X.2018.1466018.

[70] [70] STEFFIN D, GHATWAI N, MONTALBANO A,et al. Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers[J]. Nature,2025, 637(8047): 940-946. DOI:10.1038/s41586-024-08261-8.

[71] [71] INGANGI V, DE CHIARA A, FERRARA G,et al. Emerging treatments targeting the tumor microenvironment for advanced chondrosarcoma[J/OL]. Cells, 2024, 13(11): 977[2025-03-22]. https://pubmed.ncbi.nlm.nih.gov/38891109/. DOI:10.3390/cells13110977.