Precision Cancer Medicine:ex Vivo Primary Cells And Patient-derived Tumor Xenograft Models Drug Sensitivity Testing

Malignant tumor is a major threat to human health with highly morbidity and mortality and is the leading cause of death worldwide.Tumor is a highly heterogeneous disease whose inherent complexity has severely stymied tumor therapies.Epithelial sarcoma is rare and highly heterogeneous malignant soft tissue tumor with high tendency recurrence and metastases.The pathogenesis of epithelial sarcoma is unclear.Chemotherapy is the major first-line therapeutics against epithelial sarcoma.However,the sensitivity of the same drug presented different effect on the various subtypes of tumor;even to the same subtype,it exerted difference in individual suffering.In addition,the unknown sensitivity of chemotherapy drugs long-term used will produce toxic side effects and drug resistance in patient,it is the mainly challenge of clinical treatment.We separated the primary tumor cells of epithelioid sarcoma from the clinical patient and established the Patient-derived xenograft(PDX)mouse models,then we screened out doxorubicin that is the sensitive drug to epithelioid sarcoma.In in vitro assay,doxorubicin presented anti-growth on primary tumor cells at very low concen-tration.In addition,combination of doxorubicin and trametinib have showed a synergistic effect.At the animal study,we found doxorubicin and trametinib suppressed tumor growth on PDX mouse models.Combination of doxorubicin and trametinib showed more significant effects than individual drug treatment.We found that combination of doxorubicin and trametinib performed the anti-tumor growth mainly through activating the PARP signaling pathway.In conclusion,we established a new epithelioid sarcoma cell line and the PDX model to detect the sensitive drugs to it.Doxorubicin has been screened and validated that is sensitive to in vitro and in vivo models of epithelioid sarcoma.At the same time,we provided a clinical reference for the chemotherapy of epithelioid soft tissue sarcoma.