Osteosarcoma (OS)
Osteosarcoma (OS) presents formidable challenges, necessitating the exploration of innovative methods to enhance diagnostics and therapy development. Our company is dedicated to pushing the boundaries in understanding and treating OS through a comprehensive suite of services, encompassing diagnostics, therapy advancement, animal model creation, and preclinical research.
Overview of Osteosarcoma (OS)
Osteosarcoma(OS) is a malignant tumor that arises from bone tissue. It primarily affects children, adolescents, and young adults, with the peak incidence occurring during the teenage years. Approximately 1000 new cases of osteosarcoma are diagnosed each year in the United States. OS often originates in long bones such as the femur, tibia, or humerus, but it can also occur in other bones.
The tumor is characterized by the abnormal proliferation of osteoblasts, the cells responsible for bone formation. OS typically presents as a painful swelling or a mass in the affected bone. It has a high propensity for metastasis to the lungs and other distant sites, making it a highly aggressive cancer.
Pathogenesis of Osteosarcoma (OS)
The exact cause of OS is not well understood, but several risk factors have been identified. These include genetic predispositions, prior exposure to radiation therapy, and certain inherited conditions such as Li-Fraumeni syndrome and Paget's disease of bone.
Research has shown that OS often involves genetic alterations, particularly in the TP53 and RB1 tumor suppressor genes. Mutations or deletions in these genes disrupt normal cell cycle regulation and DNA repair mechanisms, leading to uncontrolled growth and tumor formation.
Fig. 1 The genomic locus of the TP53 gene and its protein sequence in osteosarcoma samples. (Czarnecka, Anna M., et al., 2020)Targeted Therapies for Osteosarcoma (OS)
TP53 Targeted Therapies
The TP53 gene, commonly referred to as the "guardian of the genome," is frequently mutated or deleted in OS. It plays a critical role in regulating cell cycle arrest and apoptosis in response to DNA damage. Therapeutic strategies targeting TP53 aim to restore its tumor-suppressive functions.
RB1 Ttargeted Therapies
The RB1 gene encodes the retinoblastoma protein, which regulates cell cycle progression by inhibiting the activity of certain transcription factors. Loss of RB1 function is also observed in OS, leading to uncontrolled cell proliferation. Targeting RB1 and its associated pathways offers potential therapeutic avenues.
MAPK Targeted Therapies
The Mitogen-Activated Protein Kinase (MAPK) pathway, including proteins like ERK, JNK, and p38, plays a crucial role in cell growth, differentiation, and survival. Dysregulation of this pathway has been implicated in OS. Targeting components of the MAPK pathway holds promise for therapeutic intervention.
Wnt/β-catenin Targeted Therapies
The Wnt signaling pathway, particularly the aberrant activation of β-catenin, is involved in OS pathogenesis. In normal cells, this pathway regulates cell fate decisions and embryonic development. Targeting the Wnt/β-catenin pathway may offer opportunities to inhibit OS progression.
Table 1 Protein targets and potential drugs for OS. (Czarnecka, Anna M., et al., 2020)
| Protein | Potential Drug |
|---|---|
| DNMT1 (DNA (cytosine-5)-methyltransferase 1) | azacytidine (Vidaza), decitabine (Dacogen) |
| ERBB2 (receptor tyrosine-protein kinase erbB-2) | trastuzumab (Herceptin), lapatinib (Tycerb), afatinib (GIOTRIF/GILOTRIF), pertuzumab (PERJETA) |
| GSR (mitochondrial glutathione reductase | carmustine (GLIADEL® WAFER) |
| HDAC1 (histone deacetylase 1) | vorinostat (Zolinza) |
| HDAC2 (histone deacetylase 2) | romidepsin (Istodax) |
| KIT (mast/stem cell growth factor receptor kit) | imatinib (Gleevec), sorafenib (Nexavar), sunitinib (Sutent), pazopanib (Votrient), dasatinib (Sprycel), axitinib (Inlyta), nilotinib (Tasigna) |
| FGFR1 (fibroblast growth factor receptor 1) | lenvatinib (Lenvima) |
| MET (hepatocyte growth factor receptor) | cabozantinib (COMETRIQ), crizotinib (XALKORI) |
| MTOR (serine/threonine protein kinase mTOR) | temsirolimus (Torisel), everolimus (Afinitor) |
| PARP1 (poly (ADP–ribose) polymerase 1) | olaparib (AZD2281) |
| PDGFR α (platelet-derived growth factor receptor alpha) | imatinib (Gleevec), sorafenib (Nexavar), sunitinib (Sutent), pazopanib (Votrient), nilotinib (Tasigna), axitinib (Inlyta) and dasatinib (Sprycel) |
| PSMC2 (26S protease regulators subunit 7) | bortezomib (Velcade) |
Our Services
At our company, we are dedicated to advancing the development of diagnostics and therapies for osteosarcoma (OS). Our comprehensive range of services includes target identification and validation, drug discovery and development, preclinical testing and evaluation.
Therapy Development Platforms
Animal Models of Osteosarcoma (OS)
| Genetic Engineering Model Development | ||
| Genetically engineered models (GEMs) have revolutionized cancer research, including the study of osteosarcoma (OS). Our company offers exceptional genetic engineering model development services, facilitating the investigation of key genetic alterations associated with OS, including conditional knockout models and transgenic models. | ||
| Optional Genetic Modifications | p53, Rb, shp53, or SV40 Tag | |
| Optional Species | Mouse, Rat, Dog, Others | |
In addition, we also provide other customized animal models to meet diverse needs. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Czarnecka, Anna M., et al. "Molecular biology of osteosarcoma." Cancers 12.8 (2020): 2130.
- Smrke, Alannah, et al. "Future directions in the treatment of osteosarcoma." Cells 10.1 (2021): 172.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.