Identifying States of Collateral Sensitivity during the Evolution of Therapeutic Resistance in Ewing's Sarcoma

iScience

Andrew Dhawan¹  Jacob G. Scott²  Erin McClure²  Arda Durmaz³  Stephen L. Lessnick⁴  Jessica A. Scarborough⁵  Masahiro Hitomi⁵  Peter Anderson⁵ 

[1] Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA;Systems Biology and Bioinformatics Department, School of Medicine, Case Western Reserve University, Cleveland OH 44106, USA;Heme/Onc/BMT, Cleveland Clinic, Cleveland, OH 44106, USA;Neurological Institute, Cleveland Clinic, Cleveland, OH 44106, USA;Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA;

关键词: Biological Sciences;    Evolutionary Biology;    Cancer Systems Biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Advances in the treatment of Ewing's sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path toward collateral sensitivity is not always repeatable, nor is there always a clear trajectory toward resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for patients with EWS.

【 授权许可】

Unknown