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New molecular insights into osteosarcoma targeted therapy.

AbstractPURPOSE OF REVIEW:
Recent translational studies in osteosarcoma are discussed with the purpose to shed light on the new molecular therapeutic targets.
RECENT FINDINGS:
The genetic aberrations of vascular endothelial growth factor (VEGF), mammalian target of rapamycin, Wnt signaling pathway, the inactivation of p53, Rb, WWOX genes, and amplification of APEX1, c-myc, RECQL4, RPL8, MDM2, VEGFA might be involved in the pathogenesis of osteosarcoma. The promising therapeutic targets for osteosarcoma patients include: integrin, ezrin, statin, NOTCH/HES1, matrix metalloproteinases (MMPs), m-calpain, and Src, which are involved in tumor cell invasion and metastasis; aldolase A, fructose-bisphosphate, sulfotransferase family 3A, member 1, BCL2-associated athanogene 3, heat shock protein 70 (HSP70), B-cell lymphoma 2-interacting mediator (BIM), polo-like kinase 1, hypoxia inducible factor 1, alpha subunit, minibrain-related kinase, Bcl-xl, caspase-3, midkine, high mobility group box 1 protein (HMGB1), and Beclin1, which are involved in tumor proliferation and apoptosis; met proto-oncogene (hepatocyte growth factor receptor), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, insulin-like growth factor (IGF)-1R, fms-related tyrosine kinase 4, platelet-derived growth factor receptor, beta polypeptide, IGF-I/II, and c-kit, which are involved in tumor growth; endosialin, VEGF, thrombin, and MMPs, which are involved in tumor angiogenesis; transforming growth factor-α/β, parathyroid hormone-like hormone, interleukin-6, interleukin-11, receptor activator of nuclear factor-κB ligand, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1, and cathepsin, which are involved in osteoclast function; Myc, HSP90, p-Met, p-Akt, p-STAT3, and cyclin D1, which are transcriptional factors; p-GP, hydroxysteroid (17-beta) dehydrogenase 10, HMGB1, BIM, inorganic phosphate, Bcl-2, PARP, mdm2, p21, Bax, and mitogen-activated protein kinase 1, which are involved in drug sensitivity. Furthermore, microRNAs such as miR-215 are also therapeutic targets.
SUMMARY:
These translational studies in osteosarcoma have identified new molecular targets for osteosarcoma.
AuthorsJilong Yang, Wei Zhang
JournalCurrent opinion in oncology (Curr Opin Oncol) Vol. 25 Issue 4 Pg. 398-406 (Jul 2013) ISSN: 1531-703X [Electronic] United States
PMID23666471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antineoplastic Agents
  • MAS1 protein, human
  • Proto-Oncogene Mas
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Bone Neoplasms (drug therapy, genetics, metabolism)
  • Humans
  • Molecular Targeted Therapy
  • Osteosarcoma (drug therapy, genetics, metabolism)
  • Proto-Oncogene Mas

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