Methods for the treatment of hrd cancer and brca-associated cancer

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment of cancer, particularly BRCA-associated cancer and chemo-resistance BRCA-associated cancer. The inventors investigated the role of NMNAT1 in cancer, particularly in BRCA-associated cancer. The inventors demonstrated that NMNAT1 inhibition kills BRCA1 and BRCA2-mutated tumor cells but does not affect the survival of non-BRCA-mutated cells. The inventors also demonstrated that NMNAT1, a nuclear enzyme other than PARP1, is crucial for the survival of HRD cells and indicate that NMNAT1 is a key factor which activities are necessary for the survival of HRD cells. The inventors also demonstrated that inhibition of NMNAT1 kills PARP-inhibitor and cisplatin-resistant BRCA1 and BRCA2-mutated tumors and show that targeting NMNAT1 kills chemo-resistance HRD cells, particularly PARPi-resistant HRD cells. Altogether, the present invention highlights the role of NMNAT1 inhibitors in cancer and the use of NMNAT1 inhibitors in the treatment of cancer, particularly BRCA-associated cancer including BRCA-associated cancer with acquired drug resistance in mono- or combination therapy with PARPi. In the present invention, the inventors provide in vitro evidences towards a direct role of NMNAT1 in BRCA-associated cancer. Thus, the present invention relates to NMNAT1 inhibitor for use in the treatment of cancer, particularly HRD cancer. BRCA-associated cancer and chemo-resistance BRCA-associated cancer.

Dependencies are inferred from the claim text.