Methods and composition to identify and treat subjects resisting to chemotherapy treatment

The present invention relates to a method for treating a subject suffering from a cancer comprising a step of administering said subject with a therapeutically effective amount of an inhibitor of NETs. By in vitro experiments, inventors have demonstrated that inhibiting the formation of NETs with a PAD4 inhibitor or digesting the NET-DNA scaffold with DNase I during PMAinduced NET formation overcame the chemoresistance induced by the NET CM in vitro. They have also generated data in vivo and shown that targeting of NETs with either a PAD4 inhibitor or DNase I enhanced chemotherapy efficacy. PAD4 inhibition and DNase I treatment not only eliminated NETs in the metastatic lungs and in the plasma, but also reduced neutrophil recruitment to the lungs.

Keywords: Metastasis, Breast Cancer, Chemotherapy resistance
Cancer Cell. 2023 Apr 10;41(4):757-775.e10. doi:10.1016/j.ccell.2023.03.008.

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