Epigenetic Therapy to Overcome Checkpoint Adaptation in Rhabdomyosarcoma

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Alveolar rhabdomyosarcoma (aRMS) is a cancer of the soft tissues. In many cases, the disease responds to chemotherapy, but in other patients our current treatment options fail and the cancer spreads throughout the body–a deadly outcome. Our team has identified a cancer-causing gene (also known as an oncogene) called Pax3:Foxo1 that causes current treatments to fail. Remarkably, Pax3:Foxo1 can silenced by entinostat, a drug recently granted FDA breakthrough designation for breast cancer.

In our studies, entinostat dramatically improved sensitivity to the rhabdomyosarcoma chemotherapeutic, Actinomycin-D. What remains to be established is whether entinostat will sensitize Pax3:Foxo1+ aRMS to the chemotherapies most often used in relapsed disease. Our project will identify whether silencing this gene will make relapsed aRMS sensitive to combined chemotherapy, paving the way for an evidence-based clinical trial that could save lives.


Our Goal

Establish entinostat as complimentary drug for relapsed alveolar rhabdomyosarcoma so the combination therapy can be tested out in clinical trials and developed into widely available treatment.


Our Timeline:

A phase I study of entinostat to find the safe dose in children will start in 2016. However, this 18-24 month project to further validate entinostat as a drug for rhabdomyosarcoma must be completed before entinostat can be given to patients for a phase II study of its effectiveness against rhabdomyosarcoma. Once funded, our work will take 18-24 months to complete.


Our Partners:

This project has the collaborative support of the Children’s Oncology Group Phase I and Soft Tissue Sarcoma committee chairpersons, and the cooperation of Syndax Pharmaceuticals.

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