Ewing sarcoma tumors can be split into two groups for targeted care
Purpose: Targeted cancer therapeutics have not significantly benefited Ewing sarcoma patients with metastatic or relapsed disease. Understanding the molecular underpinnings of drug-resistance can lead to biomarker-driven treatment selection. Experimental Design: Receptor tyrosine kinase pathway activation was analyzed in tumor cells derived from a panel of Ewing sarcoma tumors, including primary and metastatic tumors from the same patient.
In one IGF1R was predominantly nuclear , DNA damage tolerance pathway was upregulated, cells had low replication stress and RRM2B levels, and high levels of WEE1 and RAD21. These tumors were relatively insensitive to IGF1R inhibition. The second group had high replication stress and RRM2B, low levels of WEE1 and RAD21, membrane-associated IGF1R signaling, and sensitivity to IGF1R or WEE1-targeted inhibitors.
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