Origin and Therapies of Osteosarcoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Clinical Features
3. Diagnosis
4. Classification of OS
- -
- Extent of the primary tumor (T): T1 refers to a tumor that is confined to the bone (intra-compartmental), and T2 refers to a tumor that affects surrounding structures (extra-compartmental).
- -
- Metastasis (M): M1 indicates that a tumor has spread to nearby lymph nodes. M0 indicates no spread to lymph nodes.
- -
5. Current Therapies for OS
5.1. Chemotherapy
5.2. Surgery
6. Limitations of Current Treatments
7. Genetic Disorders in OS
8. Osteosarcoma Models
9. The Vicious Cycle Hypothesis in OS
10. New Therapeutic Approaches in OS
10.1. Immunotherapy
10.1.1. Targeting Cell Surface Proteins
10.1.2. Checkpoint Inhibitors
10.2. Bone Resorption Inhibition
10.3. Targeting Receptor Tyrosine Kinases and Intracellular Signaling
Target Cell, Gene or Protein | Agent Used | Reference |
---|---|---|
Targeting Receptor Tyrosine Kinases and Intracellular Signaling | ||
PDGFRα and β, cKIT, Axl, RYK, EGFR, EphA 2 and 10, IGF1R | Imatinib (STI571) | [259,261,262,263] |
c-KIT, Epha2 and PDGFRβ RTK inhibitor | Dasatinib | [264,265] |
Met (HGFr) | PF-2341066 | [266] |
VEGFR, PDGFR, RET and c-Kit | Sorafenib | [267,268,269] |
VEGFRs | Bevacizumab | [257] |
IGF-1R | Cixutumumab | [177] |
VEGFR, PDGFR, KIT, FGFR and RET | Regorafenib | [270,271] |
VEGFR, KIT, RET, AXL and PDGFR | Cabozantinib | [272] |
VEGFR, PDGFR, KIT, FGFR and RET | Lenvatinib | [273] |
VEGF, PDGFR and KIT | Pazopanib | [274] |
Src | Saracatinib (AZD0530) | [278] |
mTOR | Ridaforolimus | [284,285] |
mTOR and DNA-PK | CC-115 | [286,287] |
Immunomodulation | ||
immune system | IFN-α-2b | [25,162] |
lymphocytes | IL-2 | [164,165] |
Monocytes and macrophages | Mifamurtide | [167,168] |
Targeting surface proteins | ||
HER2 | Trastuzumab | [174] |
Trastuzumab deruxtecan | NCT04616560 | |
IGF-1/IGF-1R | R1507 | NCT00642941 [176] |
Cixutumumab | [177,178] | |
GD2 | Dinutuximab + Sargramostim | NCT02484443 [181] |
humanized bispecific anti-GD2 antibody 3F8 (Hu3F8-BsAb) | NCT03860207 | |
activated T cells armed with a bispecific GD2 antibody | NCT02173093 [184] | |
LRRC15 | ABBV-085 | NCT02565758 [187] |
B7-H3 | Omburtanab | NCT00089245 |
DS-7300a | NCT04145622 | |
Checkpoint inhibitors | ||
CTLA-4 | Ipilimumab | [202] |
PD-1 | Pembrolizumab | [211] |
Nivolumab | NCT04803877 [210] | |
PD-L1 | Avelumab | NCT03006848 [212] |
Bone resorption inhibition | ||
RANKL | Denosumab | [217,222] |
Hydroxyapatite | Zoledronate | [227,228,230,232,233,281] |
Zoledronate + chemotherapy | [55] | |
Zoledronate + sirolimus | NCT02517918 (METZOLIMOS) |
11. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Stage | Grade | Tumor | Metastasis |
---|---|---|---|
IA | G1 | T1 | M0 |
IB | G1 | T2 | M0 |
IIA | G2 | T1 | M0 |
IIB | G2 | T2 | M0 |
III | G1 or G2 | T1 or T2 | M1 |
Stage | Grade | Primary Tumor Size | Lymph Nodes Metastasis | Distant Metastasis |
---|---|---|---|---|
IA | Low | <8 cm | N0 | M0 |
IB | Low | >8 cm | N0 | M0 |
IIA | High | <8 cm | N0 | M0 |
IIB | High | >8 cm | N0 | M0 |
III | Any grade | Any size | N0 | M0 |
IVA | Any grade | Any size | N0 | M1a |
IVB | Any grade | Any size | N1 | Any M |
Cells | Origin | Gender | Age | Location | Model in Mice | p53 Status | Reference |
---|---|---|---|---|---|---|---|
MG-63 | human | male | 14 | Bone | Yes | rearranged | [129] |
Saos-2 | human | female | 11 | Bone | Yes | null | [130] |
U2OS | human | female | 15 | Tibia | Yes | WT inactivated | [131] |
MMNG-HOS | human | female | 13 | Femur | Yes | R156P;F270L | [132] |
143-B HOS | human | female | 13 | Femur | Yes | R156P;F270L | [133] |
CAL-72 | human | male | 10 | Knee recurrence | No | WT | [134] |
G-292 | human | female | 9 | Bone | ND | [135] | |
SJSA-1 | human | male | 19 | Femur | ND | P53 and MDM2 amplification | [136] |
K7M2 | BALB/c mice | ND | ND | ND | syngenic | [137] | |
POS-1 | C3H/He mice | ND | ND | ND | syngenic | WT | [138] |
MOS-J | C57BL/6J mouse | ND | ND | ND | syngenic | [139] | |
OSRGA | Rat (Sprague Dawley) | ND | ND | ND | Syngenic in rat | WT | [140] |
UMR-106 | Rat (Sprague Dawley) | ND | ND | ND | Syngenic in rat | WT | [141] |
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Moukengue, B.; Lallier, M.; Marchandet, L.; Baud’huin, M.; Verrecchia, F.; Ory, B.; Lamoureux, F. Origin and Therapies of Osteosarcoma. Cancers 2022, 14, 3503. https://doi.org/10.3390/cancers14143503
Moukengue B, Lallier M, Marchandet L, Baud’huin M, Verrecchia F, Ory B, Lamoureux F. Origin and Therapies of Osteosarcoma. Cancers. 2022; 14(14):3503. https://doi.org/10.3390/cancers14143503
Chicago/Turabian StyleMoukengue, Brice, Morgane Lallier, Louise Marchandet, Marc Baud’huin, Franck Verrecchia, Benjamin Ory, and Francois Lamoureux. 2022. "Origin and Therapies of Osteosarcoma" Cancers 14, no. 14: 3503. https://doi.org/10.3390/cancers14143503