Cancer Stem Cells as a Source of Drug Resistance in Bone Sarcomas

Journal of Clinical Medicine

Sofía T. Menéndez¹  Dzohara Murillo¹  Aida Rodríguez¹  Borja Gallego¹  René Rodríguez¹ 

[1] Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma s/n, 33011 Oviedo, Spain;

关键词: bone sarcoma;    osteosarcoma;    cancer stem cells;    drug resistance;    stemness signaling;    tumor microenvironment;   

DOI  :  10.3390/jcm10122621

来源: DOAJ

【 摘 要 】

Bone sarcomas are commonly characterized by a high degree of intra-tumor heterogeneity, which in part is due to the presence of subpopulations of tumor cells presenting stem cell properties. Similar to normal stem cells, these cancer stem cells (CSCs) display a drug resistant phenotype and therefore are responsible for relapses and tumor dissemination. Drug resistance in bone sarcomas could be enhanced/modulated during tumor evolution though the acquisition of (epi)-genetic alterations and the adaptation to changing microenvironments, including drug treatments. Here we summarize findings supporting the involvement of pro-stemness signaling in the development of drug resistance in bone sarcomas. This include the activation of well-known pro-stemness pathways (Wnt/β-Cat, NOTCH or JAT/STAT pathways), changes in the metabolic and autophagic activities, the alteration of epigenetic pathways, the upregulation of specific non-coding RNAs and the crosstalk with different microenvironmental factors. This altered signaling is expected to be translated to the clinic in the form of biomarkers of response and new therapies able to overcome drug resistance.

【 授权许可】

Unknown