The second most frequent malignant tumor of the bone after osteosarcoma, chondrosarcoma is subdivided in conventional type, mesenchymal, clear cell, and the dedifferentiated subtype. Each of these pathological entities has a particular clinical behavior. For most, surgery remains the sole valid option. However, efficient systemic therapy options for advanced and metastatic cases are scarce. This short review is aimed at describing the latest options presented by current literature in these cases. Most of the data is derived from preclinical trials, but some drugs were also included in clinical research as far as phase two trials. After reviewing this data, it could be concluded that the future in unresectable or metastatic chondrosarcoma is personalized medicine and that more specific biomarkers to aid the choice are necessary.
If the inline PDF is not rendering correctly, you can download the PDF file here.
1. Murphey MD Walker EA Wilson AJ Kransdorf MJ Temple HT Gannon FH. From the archives of the AFIP: imaging of primary chondrosarcoma: radiologicpathologic correlation. Radiographics. 2013; 23(5)1245–1278.
2. Meijer D De Jong D Pansuriya TC et al.Genetic characterization of mesenchymal clear cell and dedifferentiated chondrosarcoma. Genes Chromosomes Cancer. 2012; 51(10) 899–909.
3. Mavrogenis AF Gambarotti M Angelini A et al. Chondrosarcomas revisited. Orthopedics. 2012; 35(3)e379–e390.
4. Van Maldegem AM Bovee JV Gelderblom H. Comprehensive analysis of published studies involving systemic treatment for chondrosarcoma of bone between 2000 and 2013. Clin. Sarcoma Res. 2014; 411.
5. Frezza AM Cesari M Baumhoer D et al. Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. Eur. J. Cancer. 2015; 51(3)374–381.
6. Montero JC Seoane S Ocana A Pandiella A. Inhibition of SRC family kinases and receptor tyrosine kinases by dasatinib: possible combinations in solid tumors. Clin. Cancer Res. 2011; 17(17) 5546–5552.
7. Perez J Decouvelaere AV Pointecouteau T et al. Inhibition of chondrosarcoma growth by mTOR inhibitor in an in vivo syngeneic rat model. PLoS ONE. 2012; 7(6)e32458.
8. Rubin LL De Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev. Drug Discov. 2006; 5(12)1026–1033.
9. Suijker J Oosting J Koornneef A et al. Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines. Oncotarget. 2015; 6(14)12505–12519.
10. NCCN Guidelines Version 2.2019. Bone Cancer https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf.
11. Schuetze SM Wathen JK Lucas DR et al. SARC009: Phase 2 study of dasatinib in patients with previously treated high-grade advanced sarcoma. Cancer. 2016; 122(6)868–874.
12. Van Oosterwijk JG Van Ruler MA Briaire-De Bruijn IH et al. Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells. Br. J. Cancer. 2013; 109(5)1214–1222.
13. Mccubrey JA Steelman LS Franklin RA et al. Targeting the RAF/MEK/ERK PI3K/ AKT and p53 pathways in hematopoietic drug resistance. Adv. Enzyme Regul. 2007; 4764–103.
14. Myers AP Cantley LC. Targeting a common collaborator in cancer development. Sci. Transl. Med. 2010; 2(48)48ps45.
15. Perez J Decouvelaere AV Pointecouteau T et al. Inhibition of chondrosarcoma growth by mTOR inhibitor in an in vivo syngeneic rat model. PLoS ONE. 2012; 7(6)e32458.
16. Zhang YX Van Oosterwijk JG Sicinska E et al. Functional profiling of receptor tyrosine kinases and downstream signaling in human chondrosarcomas identifies pathways for rational targeted therapy. Clin. Cancer Res. 2013; 19(14)3796–3807.
17. Tiet TD Hopyan S Nadesan P et al. Constitutive Hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am. J. Pathol. 2006; 168(1)321–330.
18. Italiano A Le Cesne A Bellera C et al. GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/ US and French National Cancer Institute Single-Arm Phase II Collaborative Study. Ann. Oncol. 2013; 24(11)2922–2926.
19. Sun Y Guo W Ren T et al. Gli1 inhibition suppressed cell growth and cell cycle progression and induced apoptosis as well as autophagy depending on ERK1/2 activity in human chondrosarcoma cells. Cell Death Dis. 2014; 5e979.
20. Kostine M Cleven AHG 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 Modern Pathology advance online publication 17 June 2016.