Molecular pathology and molecular pharmacology of osteosarcoma

Abnormalities of many tumor suppressor genes and oncogenes have been described in osteosarcoma, but separating early or primary from secondary or late genetic lesions has been difficult. Among early lesions, inactivation of both the P53 and RB pathways appears to be a central and perhaps necessary event in osteosarcomagenesis. We propose a working model for the molecular pathology of osteosarcoma and we review the numerous published studies examining the association of various molecular features with either advanced presentation, poor chemotherapy response or decreased patient survival.