Tumor-derived exosomes facilitate tumor cells escape from drug therapy in clear cell renal cell carcinoma

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers in renal cancer patients. Currently, mTOR and vascular endothelial growth factor (VEGF) inhibitors are the main targets of clinical drugs used to treat ccRCC. However, the major clinical challenge with these treatments is drug resistance. So far, the mechanisms of drug resistance in cancer are not fully understood. Methods: We applied tumor-derived exosomes to treat renal cells to detect the survival rate after co-treated with anti-tumor drugs-TNF alpha, mammalian target of rapamycin (mTOR) inhibitor or STAT3 inhibitor. Meanwhile, we also detected the expression change in the protein level related to the proliferation and exosome secretion. Results: Exosomes derived from renal carcinoma cells facilitate resistance in tumors cells when given drug therapy via the mTOR-ERK-STAT-NF-kappa B signaling pathway. Conclusions: Our results provide new insights on tumor cells resistance to drug therapies in general, and that exosomes could be the potential targets in treatment of ccRCC in future clinical