Innovative Exploratory Clinical Approaches for Relapsed and/or Refractory Metastatic Ewing’s Sarcoma

Ghisoli M, Manning L, Senzer N and Nemunaitis J

Mary Crowley Cancer Research Centers, USA
Medical Oncology and Hematology, Texas Oncology, USA
Medical City Dallas Hospital, USA
Gradalis, Inc., USA
Strike Bio, USA

^*Correspondance to: John Nemunaitis 

 PDF  Full Text Review Article | Open Access

Abstract:

Relapsed and/or refractory Ewing’s Sarcoma is a devastating pediatric disease with rapid progression and oftentimes severe side effects related to generally ineffective high dose multi-agent chemotherapy. Eighty five percent of diagnosed Ewing’s Sarcoma is characterized by EWS/FLI1 fusion gene expression that provides a unique opportunity for targeted therapeutics development. The EWS/FLI1 gene is a “driver gene” with transformative potential and integral to Ewing’s cancer progression. Although encoding a transcription factor, which is pharmacologically “undruggable”, it connects with potentially targetable molecular signals and, in addition, as a fusion gene along with accompanying tumor specific mutations provides unique neoantigens some of which process into immunogenic epitope. Very few cutting edge advances for the management and control of Ewing’s Sarcoma have been made in the last 20 years due, in part, to low incidence (one case per million people), a narrow therapeutic window, and a limited availability of tissue suitable for biomarker studies. However, recent advances in DNA/RNA manipulation [CRISPR and RNA interference (siRNA)] as well as in molecular and immune technologies have transformed both the understanding of signaling pathways and molecular mechanisms of actions and, consequently, the approach to target identification. We review the innovative exploratory approaches to five unique therapies (a EWS-FLI1 co-activator, the EWS-FLI1 fusion gene itself, a signaling receptor, a DNA damage repair component, and the antigenic matrix) currently undergoing clinical assessment in Ewing’s Sarcoma for which preliminary preclinical and clinical results suggest therapeutic benefit.

Keywords:

Cite the Article:

Ghisoli M, Manning L, Senzer N, Nemunaitis J. Innovative Exploratory Clinical Approaches for Relapsed and/or Refractory Metastatic Ewing’s Sarcoma. Clin Oncol. 2016; 1: 1079.