Work

Efficacy of the MEK1/2 inhibitor trametinib in combination with clinically-investigated γ-secretase inhibitors in rhabdomyosarcoma

Year: 2019

Type: preprint

Abstract: The childhood muscle cancer rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In the last 40 years, outcomes for low and intermediate risk patients have improved; however, high risk patients with metastatic disease still have poor overall survival. Differentiation therapy for RMS has been considered a potential clinical approach to halting tumor progression by inducing the terminal myogenic differentiation program, and thus reducing the need for cytotoxic chemotherapy. Both the NOTCH and MEK pathway have been shown to play varying roles in inducing differentiation in RMS cells. Here, we tested several different RMS cell lines harboring varying genetic abnormalities with the MEK inhibitor trametinib alone, and in combination with γ-secretase inhibitors and found no significant effect on cell viability when used together.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/622522

Authors: Megan M. Cleary, Douglas S. Hawkins, Charles Keller

Institutions: Children's Cancer Therapy Development Institute, Seattle Children's Hospital

Language: English

Topic: Sarcoma Diagnosis and Treatment

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute