Heterogeneity of Undifferentiated Pleomorphic Sarcoma Genetic Landscape: Is There a Room for Targeted Therapy?

Undifferentiated pleomorphic sarcoma (UPS) is the most morphologically and genetically heterogeneous subtype of soft tissue sarcoma. UPS could harbor multiple genetic abnormalities including activating and inactivating mutations, amplifications, chromosomal translocation, variations in the copy number of different genes. Along with less widely described epigenetic changes, multiple genetic aberrations result in numerous alterations in signaling; however, no UPS-specific targets are described. It leads to the difficulties in diagnostics, prognosis following by the development of the strategy of targeted therapy. The therapy with immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4) is the only proved targeted option for UPS due to numerous mutational events associated with activation of immune response. As nowadays UPS chemoresistance prognosis based on molecular genetics features seems insufficient, the development of experimental approaches for testing it ex vivo and in vitro may be useful for the exclusion of potentially ineffective targeted therapy courses.