Related Experiment Video
Updated: Apr 15, 2026
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Targeting the EWS-FLI1 transcription factor in Ewing sarcoma
R Tancredi1, A Zambelli, G A DaPrada
1Medical Oncology Unit, I.R.C.C.S. Salvatore Maugeri Foundation, Via Salvatore Maugeri, 10, 27100, Pavia, Italy.
Purpose:
Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS-FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies.
Methods:
Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course.
Results:
The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment.
Conclusions:
The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.
Insights
Sequential trabectedin and irinotecan showed promising results in a Ewing sarcoma patient, stabilizing the disease and improving symptoms. Further investigation of this combination therapy is warranted.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Ewing sarcoma is a rare bone cancer with limited treatment options.
- Preclinical studies suggest a synergistic effect between trabectedin and irinotecan.
- This combination targets the EWS-FLI1 transcription factor, crucial in Ewing sarcoma development.
Observation:
- A single patient with advanced Ewing sarcoma, progressing on standard therapies, received sequential trabectedin and irinotecan.
- The treatment regimen involved trabectedin infusion followed by irinotecan, administered every three weeks.
- The patient experienced transient side effects, including hematological toxicity and elevated liver enzymes.
Findings:
- Disease stabilization was achieved for 11 treatment courses.
- The patient showed clinical improvement and a reduced need for opioid pain relief.
- Sudden death occurred before the 12th course, deemed unrelated to the drug treatment.
Implications:
- The combination of trabectedin and irinotecan demonstrates encouraging clinical benefit and good tolerability in Ewing sarcoma.
- This therapeutic strategy warrants further clinical investigation for Ewing sarcoma patients.
- Targeting EWS-FLI1 may represent a viable approach in Ewing sarcoma treatment.
Related Concept Videos
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
02:38Mitogens and the Cell Cycle
01:24Regulation of Angiogenesis and Blood Supply