Development of a Circulating Tumor Cell-Based Drug Sensitivity Assay for Soft-Tissue Sarcoma( I )

Soft tissue sarcoma has an incidence of 1% in all adult cancers. The major curative treatment is radical surgery. Recurrent/metastatic (r/m) sarcoma via hematogenous spread is difficult to cure. It is very challenging to treat r/m sarcoma, because the disease consists of many histological and molecular variants that lead to a paucity of clinical evidence for precision medicine approach. Moreover, circulating sarcoma cells are not detectable by EpCAM-based capture strategy. In order to tackle the unmet need of personalizing sarcoma treatment, we develop a novel cell culture technology “eSelect” to amplify circulating sarcoma cells (CSC) from peripheral blood samples for drug sensitivity profiling. In this study, we will enroll 30 patients with r/m sarcoma in 3 years and test if eSelect results predict clinical treatment response. For cases with doxorubicin resistant disease, we will perform genetic analysis in CSC to identify the molecular basis of doxorubicin resistance. We will also test if doxorubicin-loaded platelet, a novel formulation of tumor-targeting doxorubicin delivery, may overcome doxorubicin resistance in such cells. This proposal may provide a new insight into personalized management for r/m sarcoma.