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Sarcomas, those malignant tumors emerging from transformed mesenchymal cells, stand in stark contrast to epithelial cell-originating carcinomas. These mesenchymal tumors encompass over 20% of all pediatric solid malignancies and less than 1% of all adult solid malignancies. More than 50 distinct histologic sarcoma subtypes exist amid which many do not exhibit age or location specifics. To this end, they have historically been bifurcated into two categories: those arising in bone and those arising in soft tissues inclusive of skeletal and smooth muscle, fat, vessels, peripheral nerves, tendons, ligaments, joints, and other fibrous connective tissues.
Genetically, the majority of sarcomas demonstrate nonspecific genetic changes and exhibit a complex karyotype. By contrast, approximately 30% of mesenchymal tumors manifest a specific translocation, typically with an otherwise relatively simple karyotype. Presently, more emphasis has been placed on the molecular drivers of these mesenchymal tumors leading to the identification of various genetic aberrations associated with specific sarcoma subtypes. Examples include chromosomal translocations generating fusion oncogenes (e.g., PAX3/FOXO1 in alveolar rhabdomyosarcoma, EWS-FLI1 in Ewing’s sarcoma and SYT/SSX in synovial sarcoma), gene inactivation APC in desmoid, (NF1 in malignant peripheral nerve sheath tumor), gene amplification (MDM2 and CDK4 in well- and de-differentiated liposarcoma) and specific kinase mutations (c-kit in gastrointestinal stromal tumors [GIST]). These fusion proteins act either as transcription factors up-regulating genes responsible for tumor growth, as for Ewing’s sarcoma, or translocate a highly active promoter in front of an oncogene driving tumor formation, as for aneurysmal bone cyst. Molecular studies have identified oncogenic pathways in sarcomas which can be targeted by drugs including Akt/mammalian target of rapamycin in pleomorphic sarcomas, histone deacetylases in translocation associated sarcomas of young adults, and macrophage colony-stimulating factor in synovial giant cell tumor. For many cancers, the age of the affected patient influences treatment, while sarcomas are less common.
The understanding of sarcomas in the cancer research community is rapidly increasing. The development of new drugs in sarcoma and a better understanding of the molecular pathways involved in the development and progression of sarcoma will lead to better drug selection and more personalized therapy for patients. Creative Biogene is able to offer various sarcoma pathway-related products including stable cell lines, viral particles and clones for your drug discovery projects.
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