**Part 1**

**Fundamental Aspects of Soft Tissue Tumors** 

**1** 

*Australia* 

**Considerations for Treatment Development in** 

**Rhabdomyosarcoma:** *In Vitro* **Assessment** 

Steven J. Wolf1,3, Laurence P.G. Wakelin2 and Daniel R. Catchpoole1,3 *1The Biospecimens Research Group and Tumour Bank, Children's Cancer Research Unit, The Kids Research Institute, The Children's Hospital at Westmead, Westmead, NSW,* 

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and is believed to originate from mesenchymal cells that resemble undifferentiated striated muscle cells (Wexler and Helman, 1997). It is a relatively rare tumour type with approximately 350 patients below the age of 20 diagnosed each year in the USA (Gurney et al, 1999). Incidence in Australia is also low with only 31 RMS cases out of the total 1,003 childhood cancers diagnosed between 2001 and 2005 in the state of NSW (Tracey et al 2007). Histological staining of tumour samples led to the classification of two distinct forms of tumour types: embryonal (ERMS) and alveolar (ARMS). ERMS is the most common histologically diagnosed variant of the disease and is associated with an earlier onset, most commonly around the age of 2 to 5 years (Qualman et al, 1998). Diagnosis of ERMS is made when the cells fit the criteria of appearing as stroma-rich spindle cells which are not densely packed and show no alveolar pattern of growth which characterises ARMS. Variant forms of ERMS, including botryoid and spindle cell types, have been described as being histologically

Treatment of rhabdomyosarcoma employs a multimodal approach that utilizes surgical, radiological and chemotherapeutic protocols. Unlike in the treatment of adult sarcomas, surgical removal of the tumour mass in paediatric RMS patients is usually only attempted if complete resection can be guaranteed without causing cosmetic or developmental damage to the child. For this reason chemotherapy is the frontline option in the treatment of paediatric RMS both as a means of local tumour mass control and for the prevention of residual and micrometastatic disease (Stevens, 2005). Over 70% of patients with nonmetastatic RMS will respond well to chemotherapy and reach a 5 year event free survival milestone. Patients with metastatic or stage IV ERMS however, and those with ARMS who generally present at diagnosis with an advanced metastatic form of the cancer, continue to face a poor prognosis as a result of diminished tumour response to the current chemotherapy options. Currently, less than 30% of patients with metastatic disease survive

**1. Introduction** 

similar to standard ERMS (Wexler and Helman, 1997).

**of Novel DNA Binding Drugs** 

*2The School of Medical Science, The Faculty of Medicine, The University of New South Wales, Sydney, NSW, 3Faculty of Medicine, The University of Sydney, NSW,* 
