Inhibitory Activity And Mechanism Of DCC-2036 On Proliferation And Invasion In Triple Negative Breast Cancer

Purpose: Triple negative breast cancer(TNBC)is insensitive to endocrine therapy and targeted therapy on HER-2,ER and PR.Therefore,there is a desperate need to find new targets and new targeted therapeutic drugs for TNBC.Experimental design:We evaluate the anti-tumor efficacy of the novel small molecule tyrosine kinase inhibitor DCC-2036 in TNBC cell lines and decipher the underlying mechanisms.The antiproliferation activity of DCC-2036 is also compared with other commonly used clinical drugs.Results: Our studies have confirmed that DCC-2036 could inhibit proliferation,invasion,migration,EMT as well as induce apoptosis in TNBC cells.Moreover,its antiproliferation activity was more efficient than most of clinical drugs.Besides,the combination of DCC-2036 and cisplatin or lapatinib had synergistic effect on breast cancer progression.Mechanismly,we found that DCC-2036 could target AXL / MET and then regulate the downstream PI3 K / Akt-NF?? signaling to exert its anti-tumor effect in TNBC.Conclusion: DCC-2036 has potent activity against TNBC cells by targeting AXL / MET(especially AXL)and regulating the downstream PI3 K / Akt-NF?? signaling.DCC-2036 exhibits more efficient antiproliferative activity in TNBC cells than most common clinically used drugs.