Novel strategies for the treatment of chondrosarcomas: targeting integrins.
Chondrosarcomas are a heterogeneous group of malignant bone tumors that are characterized by the production of cartilaginous extracellular matrix. They are the second most frequently occurring type of bone malignancy. Surgical resection remains the primary mode of treatment for chondrosarcomas, since conventional chemotherapy and radiotherapy are largely ineffective. Treatment of patients with high-grade chondrosarcomas is particularly challenging, owing to the lack of effective adjuvant therapies. Integrins are cell surface adhesion molecules that regulate a variety of cellular functions. They have been implicated in the initiation, progression, and metastasis of solid tumors. Deregulation of integrin expression and/or signaling has been identified in many chondrosarcomas. Therefore, the development of new drugs that can selectively target regulators of integrin gene expression and ligand-integrin signaling might hold great promise for the treatment of these cancers. In this review, we provide an overview of the current understanding of how growth factors, chemokines/cytokines, and other inflammation-related molecules can control the expression of specific integrins to promote cell migration. We also review the roles of specific subtypes of integrins and their signaling mechanisms, and discuss how these might be involved in tumor growth and metastasis. Finally, novel therapeutic strategies for targeting these molecules will be discussed.
Graduate Institute of Basic Medical Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan ; National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan.
Jui-Chieh
JC
Chen
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Orthopedic Surgery, China Medical University Hospital, Taichung 40402, Taiwan.
Yi-Chin
YC
Fong
Graduate Institute of Basic Medical Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan ; Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Biotechnology, College of Health Science, Asia University, Taichung 41354, Taiwan.
Chih-Hsin
CH
Tang
D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000235:genetics
D016023:Integrins