New approaches for pediatric rhabdomyosarcoma drug discovery: targeting combinatorial signaling.
BACKGROUND
Rhabdomyosarcomas (RMS) are rare heterogeneous pediatric tumors that are treated by surgery, chemotherapy and irradiation. New therapeutic approaches are needed, especially in the advanced stages to target the pro-oncogenic signals. Exploring the molecular interactions of the regulatory signals and their roles in the developmental aspects of different subtypes of RMS is essential to identify potential targets and develop new therapeutic drugs.


METHODS
Insights into different drug discovery approaches are discussed with specific emphasis on gene expression profiling, fusion protein, role of small interfering RNA (siRNA)- and microRNA (miRNA)-based discovery approaches, targeting cancer stem cells, and in vitro and in vivo model systems. Targeting some overexpressed signals along with the possibilities of combination therapy of validated drug targets is discussed. Additionally, methods to overcome the limitations of discovery-based research are briefly discussed.


CONCLUSIONS
Due to drug resistance, ineffective therapy in advanced stages and relapse, there is a demand to explore new drug targets and discovery approaches. Implementing miRNA-based profiling would reveal the extent of miR-based regulation, various biomarkers and potential targets in RMS. A suitable combination of innovative techniques and the use of model systems might assist the identification and validation of novel targets and drug discovery methods. Combining specific drugs along with type-specific target inhibition of overexpressed mRNAs through siRNA approaches would enable the development of personalized therapy.
University Hospital Freiburg, Center for Pediatrics and Adolescent Medicine, Clinic IV: Pediatric Hematology and Oncology, Mathildenstr. 1, 79106 Freiburg ,  Germany   +49 761 270 43000 ;  +49 761 270 45180 ;  jochen.roessler@uniklinik-freiburg.de.
Venkatesh
V
Rengaswamy
Udo
U
Kontny
Jochen
J
Rössler