Pediatric Tumor Targeting

Pediatric sarcomas account for about 15% of pediatric cancers. These sarcomas often display a highly aggressive behavior with early tendency for development of metastasis. Although current treatment regimens, including surgery and chemotherapy, can achieve good response rates, the relapse rate is generally high with extremely poor prognosis.

The significant toxicity associated with current chemotherapies generates late side effects, a major complication in pediatric oncology.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. The two main distinct histological groups with prognostic significance are embryonal RMS (ERMS) in 55% of patients, and alveolar RMS (ARMS) in 20% of patients with a five-year event-free survival of 70% for ERMS and 23% for ARMS. 

ARMS is generally the most aggressive subtype with the poorest prognosis and ERMS presenting with metastasis at diagnosis has only 30% five-year event-free survival.

Wilms tumor (WT) or nephroblastoma, is the most frequent renal tumor in childhood. Decades of clinical and basic research have helped to gradually optimize clinical care. Nowadays, curative therapy is achievable in 90% of affected children, even in those with disseminated disease.

However, relevant long-term sequelae from standard treatment such as secondary neoplasms, cardiac insufficiency, infertility, or renal diseases, call for additional and novel approaches in these situations. Yet, introduction of biology-driven approaches for risk stratification and new drug development has been slower in WT than in other childhood tumors.

Histologically three intermingled components are discernible in nephroblastoma: stroma, epithelium and blastema. Risk stratification and treatment regimen are based on disease stage and histological subtype. We defined groups at risk with event-free survival below 50%, most notably for stage IV blastemal type tumors and those displaying diffuse anaplasia

These subtypes of WT have proven relatively chemotherapy resistant including high dose therapy with stem-cell rescue, and clinicians need to use radiotherapy to overcome it, with all its long-term, potentially severe side effects especially in these very young patients.