Targeting sarcomas by proteomic approaches

Sarcomas are a group of rare and heterogeneous tumors of mesenchymal origin. From the molecular point of view, they are grouped into two main types: (i) simple karyotypes and specific chromosomal translocations, which originate gene and protein fusions; (ii) unspecific gene alterations and complex karyotypes, with numerous gains and losses. When present, chimeric proteins provide specificity in pathogenesis and sarcoma maintenance, acting either as an aberrant transcription factor or altering RNA processing. The descriptions of numerous targets, direct and indirect, emphasize the pivotal role of the fusion over the intervention of secondary events. Accordingly, the elucidation of the cell of origin becomes critical for discovering the early molecular mechanisms involved in sarcomagenesis, as well as the identification of reliable molecular markers and possible therapeutic targets. This review describes the contribution of proteomics to sarcoma research. It reflects how the elucidation of chimeric protein target networks and differential protein expression studies can play a role in identifying the mechanisms of development and progression of sarcomas, as these proteins seem to be involved in tumor metastasis, apoptosis, and other oncogenic processes. Moreover, it may be beneficial in the diagnostic clinical domain, as it may lead to biology-based therapeutic strategies for sarcomas.