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

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/beta-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.

Automated summary

Bone sarcomas are characterized by intra-tumor heterogeneity, where cancer stem cells display drug resistance and contribute to relapses and tumor dissemination. Drug resistance in bone sarcomas can be enhanced during tumor evolution through genetic alterations and adaptation to changing microenvironments. Pro-stemness signaling pathways play a role in the development of drug resistance in bone sarcomas, offering potential biomarkers and new therapies to overcome drug resistance.