Solid Tumors - role of biological agents in therapy

New tumor-targeted biological approaches to the therapy of childhood solid tumors have the promise to improve the survival of children with advanced or refractory malignancy with less acute and long term toxicity. The challenge that remains is still similar to that with chemotherapy: identifying metabolic and genetic pathways and targets that are sufficiently different or amplified in the malignant cells to allow interruption without disruption of normal cell processes, and to then synthesize molecules that will inhibit these targets without other non-specific toxicity. Great expectations were raised by the success in two forms of leukemia of agents that target a specific genetic translocation: the older results with induction of remission by all-trans retinoic acid, targeting the retinoic acid receptor, disrupted by the 15;17 translocation in acute promyelocytic leukemia, and the dramatic responses to imatinib, a small molecule targeting the bcr-abl translocation in CML. Thus far, the search for similar “druggable” genetic targets in paediatric cancers has not yet resulted in such dramatic results, though many genetic aberrations that might provide potential targets have been identified, such as the translocation with its cloned EWS-Fli1 protein in Ewing’s sarcoma or MYCN gene amplification in neuroblastoma. The far-reaching technologies brought forward by the Human Genome Project of mRNA profiling by micro-arrays now allows description of the gene expression profile of each tumor in great detail, which can then be correlated to biological or clinical characteristics of the tumors to help select new targets.