Page 280 - Haematologica March 2020

H. de Boussac et al.
PBK inhibitors could overcome Lenalidomide resistance. Even if these observations are promising, additional in vivo experiments are needed to confirm the potential and eluci- date the mechanistic roles of these kinases in Lenalidomide and Melphalan resistance reversion.
The development of the KI could be used to identify high-risk patients that could benefit from treatment with selected kinases inhibitors. Developing the KI, we also identified kinases that have already been linked to MM physiopathology including CKS1B,21 AURKA,22 CDKN2C,23 NEK251 and BUB1B.52 In addition, we also identified a num- ber of kinases (PAK2, HK2, CDC7, BUB1, CKS2, TK1, MAP2K6, NTRK3, STK39, PTPRG, CDKN3, DUSP10, PFKP, SRPK2, RPRD1A, PI4K2B) without a clear or docu- mented connection with MM, but which are considered as potential targets in other cancers. According to the high degree of heterogeneity of the disease, we look forward to the development of new inhibitors targeting these kinases,
which could be of therapeutic interest in MM.
To date, no kinase inhibitors have received the approval of the Food and Drug Administration for the treatment of MM.7 Our study demonstrates that kinase targeting could be of therapeutic interest, especially in high-risk MM patients defined by the KI. Since this index significantly increases at relapse compared to newly diagnosed patients, CHK1, MELK, PLK4, SRPK1, CDC7-DBF4, MPS1/TTK and PBK inhibitors could represent new treat- ment options alone or in combination with Melphalan or
IMiD for refractory/relapsing MM patients.
Funding
This work was supported by grants from INCa (Institut National du Cancer; PLBIO15-256), ITMO Cancer (MM&TT), ANR (TIE-Skip; 2017-CE15-0024-01), SIRIC Montpellier Cancer (INCa_Inserm_DGOS_12553) and Institut Universitaire de France.
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