| abstract |
The present invention relates to a method of treating multiple myeloma. The inventors analyzed two sets of 18 and 40 samples from symptomatic t(4; 14) MM at presentation by exome or RNA sequencing, respectively. They confirm the high mutational rates in the NRAS, KRAS, BRAF and FGFR3 genes which have been previously described, and strongly suggests that these events are mutually exclusive in t(4;14) MM. Mutations in ATM/ATR, MAPK and MYCBP2 occur at relatively high frequencies (11.4%, 14% and 8% respectively), while very few t(4;14) patients carry alterations in FAM46C or CCND1. Mutations in PRKD2, the gene coding for the PKD2 serine/threonine kinase, affect around 11.4% of the cases and this alteration is associated with progression to symptomatic myeloma in one patient. The inventors also tested the inhibition of PKD2 activity by kb NB 142-70 and the inhibition of PKD 1, PKD2 and PKD3 by CRT0066101 and observed that these agents induced cell growth arrest and apoptosis of tumor plasma cells in vitro. These results show that PKD2 and others members of the PKD family is a therapeutic target in patients with MM. Thus, the present invention relates to a PKD inhibitor for use in the treatment of multiple myeloma. |