Drug resistance in recurrent and metastatic Ewing sarcoma

Abstract

Survival of patients with recurrent and metastatic Ewing sarcoma (ES) has not markedly improved in the last 40 years; the main reason for the poor prognosis of these patients is drug resistance. However, intrinsic and acquired resistance may occur in response to both traditional chemotherapy and targeted drugs. These complex mechanisms plausibly include instability of the genetic material, enhanced drug efflux and metabolism, positive DNA repair, inhibition of tumor cell apoptosis, miRNAs, the tumor microenvironment, cancer stem cells, autophagy, and the activation of cell proliferation pathways. The development and application of nanoparticles bring new hope for reversing drug resistance in ES, accompanied with encouraging results from preclinical trials. In this review, we elucidate the molecular mechanisms underlying drug resistance in ES and propose putative strategies to overcome this resistance to improve prognosis of patients with ES.